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Zhang J, Ding W, Yin Z, Liu S, Zhao M, Xu Y, Liu J, Pan W, Peng S, Wei C, Zheng Z, Qin JJ, Wan J, Wang M. Interleukin-12p40 deficiency attenuates myocardial ferroptosis in doxorubicin-induced chronic cardiomyopathy by inhibiting Th17 differentiation and interleukin-17A production. Cardiovasc Res 2024; 120:2117-2133. [PMID: 39298642 DOI: 10.1093/cvr/cvae208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 05/07/2024] [Accepted: 08/06/2024] [Indexed: 09/22/2024] Open
Abstract
AIMS Interleukin (IL)-12p40 is a common subunit of the bioactive cytokines IL-12 and IL-23, and it also has its own intrinsic functional activity. However, its role in doxorubicin-induced chronic cardiomyopathy (DICCM) as well as the underlying mechanisms are still unknown. METHODS AND RESULTS In this study, we used IL-12p40-knockout mice, IL-23p19-knockout mice, Rag1-knockout mice, a ferroptosis inhibitor, recombinant IL-12 (rIL-12), rIL-23, rIL-12p40, rIL-12p80, and anti-IL17A to investigate the effects of IL-12p40 on DICCM and elucidate the underlying mechanisms. We found that myocardial ferroptosis were increased in DICCM and that the inhibition of ferroptosis protected against DICCM. The expression of IL-12p40 was upregulated, and IL-12p40 was predominantly expressed by CD4+ T cells in the hearts of mice with DICCM. IL-12p40 knockout attenuated cardiac dysfunction, fibrosis and ferroptosis in DICCM, and similar results were observed in the context of CD4+ T cell IL-12p40 deficiency in Rag1-/- mice. Treatment with rIL-23, but not rIL-12, rIL-12p40 monomer or rIL-12p80, abolished the protective effects of IL-12p40 knockout. Moreover, rIL-23 treatment and IL-23p19 knockout exacerbated and ameliorated DICCM, respectively. IL-12p40 knockout might protect against DICCM by inhibiting Th17 differentiation and IL-17A production but not Th1, Th2 and Treg differentiation. Neutralizing IL-17A with an antibody also attenuated cardiac dysfunction, fibrosis, and ferroptosis. The IL-12p40/Th17/IL-17A axis might promote cardiomyocyte ferroptosis by activating TNF receptor-associated factor 6 (TRAF6)/mitogen-activated protein kinase (MAPK)/P53 signalling in DICCM. CONCLUSION Interleukin-12p40 deficiency protects against DICCM by inhibiting Th17 differentiation and the production of IL-17A, which plays critical roles in cardiomyocyte ferroptosis in DICCM via activating TRAF6/MAPK/P53 signalling. Our study may provide novel insights for the identification of therapeutic targets for treating DICCM in the clinic.
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Affiliation(s)
- Jishou Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Wen Ding
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Wuhan, China
| | - Zheng Yin
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Siqi Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Mengmeng Zhao
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Yao Xu
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Jianfang Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Wei Pan
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Shanshan Peng
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Cheng Wei
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Zihui Zheng
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Juan-Juan Qin
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Department of Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan, China
- Center for Healthy Aging, Wuhan University School of Nursing, Wuhan, China
| | - Jun Wan
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Menglong Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
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Lewis AJ, Richards AC, Mendez AA, Dhakal BK, Jones TA, Sundsbak JL, Eto DS, Rousek AA, Mulvey MA. Plant phenolics inhibit focal adhesion kinase and suppress host cell invasion by uropathogenic Escherichia coli. Infect Immun 2024; 92:e0008024. [PMID: 38534100 PMCID: PMC11075462 DOI: 10.1128/iai.00080-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 03/05/2024] [Indexed: 03/28/2024] Open
Abstract
Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here, we tested a panel of four well-studied phenolic compounds-caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate-for the effects on host cell adherence and invasion by uropathogenic Escherichia coli (UPEC). These bacteria, which are the leading cause of UTIs, can bind and subsequently invade bladder epithelial cells via an actin-dependent process. Intracellular UPEC reservoirs within the bladder are often protected from antibiotics and host defenses and likely contribute to the development of chronic and recurrent infections. In cell culture-based assays, only resveratrol had a notable negative effect on UPEC adherence to bladder cells. However, both CAPE and resveratrol significantly inhibited UPEC entry into the host cells, coordinate with attenuated phosphorylation of the host actin regulator Focal Adhesion Kinase (FAK or PTK2) and marked increases in the numbers of focal adhesion structures. We further show that the intravesical delivery of resveratrol inhibits UPEC infiltration of the bladder mucosa in a murine UTI model and that resveratrol and CAPE can disrupt the ability of other invasive pathogens to enter host cells. Together, these results highlight the therapeutic potential of molecules like CAPE and resveratrol, which could be used to augment antibiotic treatments by restricting pathogen access to protective intracellular niches.IMPORTANCEUrinary tract infections (UTIs) are exceptionally common and increasingly difficult to treat due to the ongoing rise and spread of antibiotic-resistant pathogens. Furthermore, the primary cause of UTIs, uropathogenic Escherichia coli (UPEC), can avoid antibiotic exposure and many host defenses by invading the epithelial cells that line the bladder surface. Here, we identified two plant-derived phenolic compounds that disrupt activation of the host machinery needed for UPEC entry into bladder cells. One of these compounds, resveratrol, effectively inhibited UPEC invasion of the bladder mucosa in a mouse UTI model, and both phenolic compounds significantly reduced host cell entry by other invasive pathogens. These findings suggest that select phenolic compounds could be used to supplement existing antibacterial therapeutics by denying uropathogens shelter within host cells and tissues and help explain some of the benefits attributed to traditional plant-based medicines.
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Affiliation(s)
- Adam J. Lewis
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, USA
| | - Amanda C. Richards
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, USA
| | - Alejandra A. Mendez
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, USA
- School of Biological Sciences, University of Utah, Salt Lake City, Utah, USA
- Henry Eyring Center for Cell & Genome Science, University of Utah, Salt Lake City, Utah, USA
| | - Bijaya K. Dhakal
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, USA
| | - Tiffani A. Jones
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, USA
| | - Jamie L. Sundsbak
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, USA
| | - Danelle S. Eto
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, USA
| | - Alexis A. Rousek
- School of Biological Sciences, University of Utah, Salt Lake City, Utah, USA
- Henry Eyring Center for Cell & Genome Science, University of Utah, Salt Lake City, Utah, USA
| | - Matthew A. Mulvey
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, USA
- School of Biological Sciences, University of Utah, Salt Lake City, Utah, USA
- Henry Eyring Center for Cell & Genome Science, University of Utah, Salt Lake City, Utah, USA
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3
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Majchrzak-Celińska A, Studzińska-Sroka E. New Avenues and Major Achievements in Phytocompounds Research for Glioblastoma Therapy. Molecules 2024; 29:1682. [PMID: 38611962 PMCID: PMC11013944 DOI: 10.3390/molecules29071682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 03/22/2024] [Accepted: 04/04/2024] [Indexed: 04/14/2024] Open
Abstract
Phytocompounds have been evaluated for their anti-glioblastoma actions for decades, with promising results from preclinical studies but only limited translation into clinics. Indeed, by targeting multiple signaling pathways deregulated in cancer, they often show high efficacy in the in vitro studies, but their poor bioavailability, low tumor accumulation, and rapid clearance compromise their efficacy in vivo. Here, we present the new avenues in phytocompound research for the improvement of glioblastoma therapy, including the ways to enhance the response to temozolomide using phytochemicals, the current focus on phytocompound-based immunotherapy, or the use of phytocompounds as photosensitizers in photodynamic therapy. Moreover, we present new, intensively evaluated approaches, such as chemical modifications of phytochemicals or encapsulation into numerous types of nanoformulations, to improve their bioavailability and delivery to the brain. Finally, we present the clinical trials evaluating the role of phytocompounds or phytocompound-derived drugs in glioblastoma therapy and the less studied phytocompounds or plant extracts that have only recently been found to possess promising anti-glioblastoma properties. Overall, recent advancements in phytocompound research are encouraging; however, only with more 3D glioblastoma models, in vivo studies, and clinical trials it is possible to upgrade the role of phytocompounds in glioblastoma treatment to a satisfactory level.
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Affiliation(s)
- Aleksandra Majchrzak-Celińska
- Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3 Str., 60-806 Poznan, Poland
| | - Elżbieta Studzińska-Sroka
- Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3 Str., 60-806 Poznan, Poland;
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Lewis AJ, Richards AC, Mendez AA, Dhakal BK, Jones TA, Sundsbak JL, Eto DS, Mulvey MA. Plant Phenolics Inhibit Focal Adhesion Kinase and Suppress Host Cell Invasion by Uropathogenic Escherichia coli. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.11.23.568486. [PMID: 38045282 PMCID: PMC10690256 DOI: 10.1101/2023.11.23.568486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/05/2023]
Abstract
Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic and polyphenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here we tested a panel of four well-studied phenolic compounds - caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate - for effects on host cell adherence and invasion by uropathogenic Escherichia coli (UPEC). These bacteria, which are the leading cause of UTIs, can bind and subsequently invade bladder epithelial cells via an actin-dependent process. Intracellular UPEC reservoirs within the bladder are often protected from antibiotics and host defenses, and likely contribute to the development of chronic and recurrent infections. Using cell culture-based assays, we found that only resveratrol had a notable negative effect on UPEC adherence to bladder cells. However, both CAPE and resveratrol significantly inhibited UPEC entry into the host cells, coordinate with attenuated phosphorylation of the host actin regulator Focal Adhesion Kinase (FAK, or PTK2) and marked increases in the numbers of focal adhesion structures. We further show that the intravesical delivery of resveratrol inhibits UPEC infiltration of the bladder mucosa in a murine UTI model, and that resveratrol and CAPE can disrupt the ability of other invasive pathogens to enter host cells. Together, these results highlight the therapeutic potential of molecules like CAPE and resveratrol, which could be used to augment antibiotic treatments by restricting pathogen access to protective intracellular niches.
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Affiliation(s)
- Adam J. Lewis
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
| | - Amanda C. Richards
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
- School of Biological Sciences, 257 S 1400 E, University of Utah, Salt Lake City, UT 84112, USA; Henry Eyring Center for Cell & Genome Science, 1390 Presidents Circle, University of Utah, Salt Lake City, UT 84112, USA
| | - Alejandra A. Mendez
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
- School of Biological Sciences, 257 S 1400 E, University of Utah, Salt Lake City, UT 84112, USA; Henry Eyring Center for Cell & Genome Science, 1390 Presidents Circle, University of Utah, Salt Lake City, UT 84112, USA
| | - Bijaya K. Dhakal
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
| | - Tiffani A. Jones
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
| | - Jamie L. Sundsbak
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
| | - Danelle S. Eto
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
| | - Matthew A. Mulvey
- Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
- School of Biological Sciences, 257 S 1400 E, University of Utah, Salt Lake City, UT 84112, USA; Henry Eyring Center for Cell & Genome Science, 1390 Presidents Circle, University of Utah, Salt Lake City, UT 84112, USA
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de Morais MC, Medeiros GA, Almeida FS, Rocha JDC, Perez-Castillo Y, Keesen TDSL, de Sousa DP. Antileishmanial Activity of Cinnamic Acid Derivatives against Leishmania infantum. Molecules 2023; 28:molecules28062844. [PMID: 36985814 PMCID: PMC10053546 DOI: 10.3390/molecules28062844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 03/14/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023] Open
Abstract
Leishmania infantum is the etiological agent of visceral leishmaniasis (VL) in South America, the Mediterranean basin, and West and Central Asia. The most affected country, Brazil, reported 4297 VL cases in 2017. L. infantum is transmitted by female phlebotomine sand flies during successive blood meals. There are no validated vaccines to prevent the infection and the treatment relies on drugs that often present severe side effects, which justify the efforts to find new antileishmanial drugs. Cinnamic acid derivatives have shown several pharmacological activities, including antiparasitic action. Therefore, in the present study, the biological evaluation of cinnamic acid and thirty-four derivatives against L. infantum is reported. The compounds were prepared by several synthesis methods and characterized by spectroscopic techniques and high-resolution mass spectrometry. The results revealed that compound 32 (N-(4-isopropylbenzyl)cinnamamide) was the most potent antileishmanial agent (IC50 = 33.71 μM) with the highest selectivity index (SI > 42.46), followed by compound 15 (piperonyl cinnamate) with an IC50 = 42.80 μM and SI > 32.86. Compound 32 was slightly less potent and nineteen times more selective for the parasite than amphotericin B (MIC = 3.14 uM; SI = 2.24). In the molecular docking study, the most likely target for the compound in L. infantum was aspartyl aminopeptidase, followed by aldehyde dehydrogenase, mitochondrial. The data obtained show the antileishmanial potential of this class of compounds and may be used in the search for new drug candidates against Leishmania species.
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Affiliation(s)
- Mayara Castro de Morais
- Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa 58051-900, BP, Brazil
| | - Gisele Alves Medeiros
- Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa 58051-900, BP, Brazil
| | - Fernanda Silva Almeida
- Immunology of Infectious Diseases Laboratory, Department of Cellular and Molecular Biology, Federal University of Paraiba, João Pessoa 58051-900, BP, Brazil
| | - Juliana da Câmara Rocha
- Immunology of Infectious Diseases Laboratory, Department of Cellular and Molecular Biology, Federal University of Paraiba, João Pessoa 58051-900, BP, Brazil
| | - Yunierkis Perez-Castillo
- Bio-Cheminformatics Research Group and Area de Ciencias Aplicadas, Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Americas, Quito 170503, Ecuador
| | - Tatjana de Souza Lima Keesen
- Immunology of Infectious Diseases Laboratory, Department of Cellular and Molecular Biology, Federal University of Paraiba, João Pessoa 58051-900, BP, Brazil
| | - Damião Pergentino de Sousa
- Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa 58051-900, BP, Brazil
- Postgraduate Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa 58051-900, BP, Brazil
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Taysi S, Algburi FS, Taysi ME, Caglayan C. Caffeic acid phenethyl ester: A review on its pharmacological importance, and its association with free radicals, COVID-19, and radiotherapy. Phytother Res 2023; 37:1115-1135. [PMID: 36562210 PMCID: PMC9880688 DOI: 10.1002/ptr.7707] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 11/04/2022] [Accepted: 11/11/2022] [Indexed: 12/24/2022]
Abstract
Caffeic acid phenethyl ester (CAPE), a main active component of propolis and a flavonoid, is one of the natural products that has attracted attention in recent years. CAPE, which has many properties such as anti-cancer, anti-inflammatory, antioxidant, antibacterial and anti-fungal, has shown many pharmacological potentials, including protective effects on multiple organs. Interestingly, molecular docking studies showed the possibility of binding of CAPE with replication enzyme. In addition, it was seen that in order to increase the binding security of the replication enzyme and CAPE, modifications can be made at three sites on the CAPE molecule, which leads to the possibility of the compound working more powerfully and usefully to prevent the proliferation of cancer cells and reduce its rate. Also, it was found that CAPE has an inhibitory effect against the main protease enzyme and may be effective in the treatment of SARS-CoV-2. This review covers in detail the importance of CAPE in alternative medicine, its pharmacological value, its potential as a cancer anti-proliferative agent, its dual role in radioprotection and radiosensitization, and its use against coronavirus disease 2019 (COVID-19).
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Affiliation(s)
- Seyithan Taysi
- Department of Medical Biochemistry, Medical School, Gaziantep University, Gaziantep, Turkey
| | - Firas Shawqi Algburi
- Department of Medical Biochemistry, Medical School, Gaziantep University, Gaziantep, Turkey.,Department of Biology, College of Science, Tikrit University, Tikrit, Iraq.,College of Dentistry, Al-Kitab University, Altun Kupri, Iraq
| | - Muhammed Enes Taysi
- Department of Emergency Medicine, Medical School, Bolu Izzet Baysal University-Bolu, Bolu, Turkey
| | - Cuneyt Caglayan
- Department of Medical Biochemistry, Medical School, Bilecik Seyh Edebali University, Bilecik, Turkey
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Ahmed SI, Jamil S, Ismatullah H, Hussain R, Bibi S, Khandaker MU, Naveed A, Idris AM, Emran TB. A comprehensive perspective of traditional Arabic or Islamic medicinal plants as an adjuvant therapy against COVID-19. Saudi J Biol Sci 2023; 30:103561. [PMID: 36684115 PMCID: PMC9838045 DOI: 10.1016/j.sjbs.2023.103561] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/09/2022] [Accepted: 01/08/2023] [Indexed: 01/15/2023] Open
Abstract
COVID-19 is a pulmonary disease caused by SARS-CoV-2. More than 200 million individuals are infected by this globally. Pyrexia, coughing, shortness of breath, headaches, diarrhoea, sore throats, and body aches are among the typical symptoms of COVID-19. The virus enters into the host body by interacting with the ACE2 receptor. Despite many SARS-CoV-2 vaccines manufactured by distinct strategies but any evidence-based particular medication to combat COVID-19 is not available yet. However, further research is required to determine the safety and effectiveness profile of the present therapeutic approaches. In this study, we provide a summary of Traditional Arabic or Islamic medicinal (TAIM) plants' historical use and their present role as adjuvant therapy for COVID-19. Herein, six medicinal plants Aloe barbadensis Miller, Olea europaea, Trigonella foenum-graecum, Nigella sativa, Cassia angustifolia, and Ficus carica have been studied based upon their pharmacological activities against viral infections. These plants include phytochemicals that have antiviral, immunomodulatory, antiasthmatic, antipyretic, and antitussive properties. These bioactive substances could be employed to control symptoms and enhance the development of a possible COVID-19 medicinal synthesis. To determine whether or if these TAIMs may be used as adjuvant therapy and are appropriate, a detailed evaluation is advised.
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Affiliation(s)
- Shabina Ishtiaq Ahmed
- Department of Plant Biotechnology, Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), 44000, Islamabad, Pakistan
- The Standard College for Girls, 3/530 Paris Road, Sialkot Pakistan
| | - Sehrish Jamil
- The Standard College for Girls, 3/530 Paris Road, Sialkot Pakistan
| | - Humaira Ismatullah
- School of Interdisciplinary Engineering & Sciences (SINES), National University of Sciences and Technology (NUST), 44000 Islamabad, Pakistan
| | - Rashid Hussain
- Department of Biosciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan
| | - Shabana Bibi
- Department of Biosciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan
- Yunnan Herbal Laboratory, College of Ecology and Environmental Sciences, Yunnan University, Kunming 650091, China
| | - Mayeen Uddin Khandaker
- Center for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, Bandar Sunway 47500, Selangor, Malaysia
| | - Aisha Naveed
- Caribbean Medical University, Willemastad, Curacao-Caribbean Island, Curaçao
| | - Abubakr M. Idris
- Department of Chemistry, College of Science, King Khalid University, Abha 62529, Saudi Arabia
- Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha 62529, Saudi Arabia
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
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Gazim ZC, Valle JS, Carvalho dos Santos I, Rahal IL, Silva GCC, Lopes AD, Ruiz SP, Faria MGI, Piau Junior R, Gonçalves DD. Ethnomedicinal, phytochemical and pharmacological investigations of Baccharis dracunculifolia DC. (ASTERACEAE). Front Pharmacol 2022; 13:1048688. [PMID: 36518668 PMCID: PMC9742423 DOI: 10.3389/fphar.2022.1048688] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 11/14/2022] [Indexed: 09/29/2023] Open
Abstract
Baccharis dracunculifolia DC (Lamiaceae) (Asteraceae) is found in South America, mainly in Argentina, Brazil, Bolivia, Paraguay and Uruguay. Folk medicine is used as a sedative, hypotensive, bronchodilator, cardiovascular disorders, anti-flu, and also in skin wounds. Considered the main source of green propolis, which increases the pharmacological interest in this species. It is also known as a "benefactor" plant facilitating the development of other plant species around it, being indicated for the recovery of degraded areas. This species has been studied for decades in order to isolate and identify the active principles present in the aerial parts (leaves and flowers) and roots. The present study consists of a review of the scientific literature addressing the ethnobotanical, ethnomedicinal, phytochemical, pharmacological and potential cytotoxic effects of the B. dracunculifolia species. In this survey, we sought to investigate issues related to the botanical and geographic description of the species, the ethnobotanical uses, as well as the phytochemical studies of the essential oil, extracts and green propolis obtained from the aerial parts and roots of B. dracunculifolia. Using high precision analytical tools, numerous compounds have already been isolated and identified from leaves and flowers such as the flavonoids: naringenin, acacetin, dihydrokaempferol, isosakuranetin and kaempferide; phenolic acids: p-coumaric, dihydrocoumaric, ferulic (E)-cinnamic, hydroxycinnamic, gallic, caffeic, and several caffeoylquinic acids derivatives; phenolic acids prenylated: artepillin C, baccharin, drupanin; the glycosides dracuculifosides and the pentacyclic triterpenoids: Baccharis oxide and friedelanol. The predominant class in the essential oil of leaves and flowers are terpenoids comprising oxygenated monoterpenes and sesquiterpenes, highlighting the compounds nerolidol, spathulenol, germacrene D and bicyclogermacrene. These compounds give the species high antimicrobial, antioxidant, antitumor, analgesic, immunomodulatory and antiparasitic potential, making this species a promising herbal medicine. In vitro toxicity assays with B. dracunculifolia extract showed low or no cytotoxicity. However, in vivo analyses with high doses of the aqueous extract resulted in genotoxic effects, which leads us to conclude that the toxicity of this plant is dose-dependent.
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Affiliation(s)
- Zilda Cristiani Gazim
- Chemistry Laboratory of Natural Products, Graduate Program in Animal Science and Biotechnology Applied to Agriculture, Paranaense University, Umuarama, Brazil
- Preventive Veterinary Medicine and Public Health Laboratory, Postgraduate Program in Animal Science with an Emphasis on Bioactive Products, Paranaense University, Umuarama, Brazil
| | - Juliana Silveira Valle
- Preventive Veterinary Medicine and Public Health Laboratory, Postgraduate Program in Animal Science with an Emphasis on Bioactive Products, Paranaense University, Umuarama, Brazil
- Molecular Biology Laboratory, Graduate Program in Animal Science and Biotechnology Applied to Agriculture, Paranaense University, Umuarama, Brazil
| | - Isabela Carvalho dos Santos
- Preventive Veterinary Medicine and Public Health Laboratory, Postgraduate Program in Animal Science with an Emphasis on Bioactive Products, Paranaense University, Umuarama, Brazil
| | - Isabelle Luiz Rahal
- Chemistry Laboratory of Natural Products, Graduate Program in Animal Science and Biotechnology Applied to Agriculture, Paranaense University, Umuarama, Brazil
| | - Gabriela Catuzo Canonico Silva
- Chemistry Laboratory of Natural Products, Graduate Program in Animal Science and Biotechnology Applied to Agriculture, Paranaense University, Umuarama, Brazil
| | - Ana Daniela Lopes
- Agricultural Microbiology and Nematology Laboratory, Graduate Program in Biotechnology Applied to Agriculture, Paranaense University, Umuarama, Brazil
| | - Suelen Pereira Ruiz
- Laboratory of Biotechnology of Plant Products and Microorganisms, Postgraduate Program in Biotechnology Applied to Agriculture, Paranaense University, Umuarama, Brazil
| | - Maria Graciela Iecher Faria
- Laboratory of Biotechnology of Plant Products and Microorganisms, Postgraduate Program in Biotechnology Applied to Agriculture, Paranaense University, Umuarama, Brazil
| | - Ranulfo Piau Junior
- Preventive Veterinary Medicine and Public Health Laboratory, Postgraduate Program in Animal Science with an Emphasis on Bioactive Products, Paranaense University, Umuarama, Brazil
| | - Daniela Dib Gonçalves
- Preventive Veterinary Medicine and Public Health Laboratory, Postgraduate Program in Animal Science with an Emphasis on Bioactive Products, Paranaense University, Umuarama, Brazil
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9
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Kuramoto H, Nakanishi T, Takegawa D, Mieda K, Hosaka K. Caffeic Acid Phenethyl Ester Induces Vascular Endothelial Growth Factor Production and Inhibits CXCL10 Production in Human Dental Pulp Cells. Curr Issues Mol Biol 2022; 44:5691-5699. [PMID: 36421669 PMCID: PMC9689326 DOI: 10.3390/cimb44110385] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/11/2022] [Accepted: 11/14/2022] [Indexed: 07/29/2023] Open
Abstract
The survival rate of root non-vital teeth is lower than that of vital teeth. Therefore, to preserve the dental pulp is very important. The vascular endothelial growth factor (VEGF) is the most potent angiogenic factor involved in the vitality of dental pulp including reparative dentin formation. Caffeic acid phenethyl ester (CAPE) is a physiologically active substance of propolis and has some bioactivities such as anti-inflammatory effects. However, there are no reports on the effects of CAPE on dental pulp inflammation. In this study, we investigated the effects of CAPE on VEGF and inflammatory cytokine production in human dental pulp cells (HDPCs) to apply CAPE to an ideal dental pulp protective agent. We found that CAPE induced VEGF production from HDPCs. Moreover, CAPE induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases (ERK), and stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) in HDPCs. Furthermore, CAPE inhibited C-X-C motif chemokine ligand 10 (CXCL10) production in Pam3CSK4- and tumor necrosis factor-alpha (TNF-α)-stimulated HDPCs. In conclusion, these results suggest that CAPE might be useful as a novel biological material for vital pulp therapy by exerting the effects of VEGF production and anti-inflammatory activities.
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10
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Arigò A, Russo M, Testa Camillo MR, Dugo P, Mondello L, Zoccali M. Supercritical fluid chromatography-tandem mass spectrometry of oxygen heterocyclic compounds in Citrus essential oils. Anal Bioanal Chem 2022; 414:4821-4836. [PMID: 35536412 DOI: 10.1007/s00216-022-04105-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/19/2022] [Accepted: 04/27/2022] [Indexed: 11/28/2022]
Abstract
Oxygen heterocyclic compounds are secondary metabolites mainly present in the non-volatile fraction of cold-pressed Citrus essential oils. Under this denomination are included coumarins, furocoumarins, and polymethoxyflavones. These compounds possess numerous beneficial properties for human health, but the ingestion of large amounts of coumarins is often related to toxic effects, whereas the phototoxicity caused by furocoumarins and UVA exposure has been well known for a long time. This research has been aimed at the validation of an analytical approach, based on supercritical fluid chromatography coupled to tandem mass spectrometry, for the analysis of OHCs in Citrus essential oils. Among eight columns tested, packed with different stationary phases, the pentafluorophenyl allowed the best baseline separation in 8 min and by using less than 10% of methanol. Calibration curves of twenty-eight standards (coumarins, furocoumarins, polymethoxyflavones) were constructed on spiked lemon distilled essential oil and the method was validated according to the EURACHEM guidelines, by calculating linearity, limit of detection (LoD), limit of quantification (LoQ), accuracy, intra-day, and inter-day precision. Specifically, recoveries were in the 80.0-118.6% range, regression coefficients were between 0.9904 and 0.9998, the LoDs were in the 0.0004-0.0470 mg kg-1 range, the LoQs were in the 0.0014-0.1536 mg kg-1 range, and coefficients of variation were between 0.3 and 2.6% (intra-day) and 1.1 and 7.4% (inter-day). The quantitative profiles of thirteen cold-pressed Citrus essential oils were determined.
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Affiliation(s)
- Adriana Arigò
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Marina Russo
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
| | - Maria Rita Testa Camillo
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Paola Dugo
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.,Chromaleont S.R.L., c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Luigi Mondello
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.,Chromaleont S.R.L., c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.,Department of Sciences and Technologies for Human and Environment, University Campus Bio-Medico of Rome, Rome, Italy
| | - Mariosimone Zoccali
- Department of Mathematical and Computer Science, Physical Sciences and Earth Sciences, University of Messina, Messina, Italy
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11
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Design and synthesis of novel caffeic acid phenethyl ester (CAPE) derivatives and their biological Activity studies in glioblastoma (GBM) cancer cell lines. J Mol Graph Model 2022; 113:108160. [DOI: 10.1016/j.jmgm.2022.108160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 01/16/2022] [Accepted: 02/14/2022] [Indexed: 12/20/2022]
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12
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Molecular Insights into the Antistress Potentials of Brazilian Green Propolis Extract and Its Constituent Artepillin C. Molecules 2021; 27:molecules27010080. [PMID: 35011307 PMCID: PMC8746355 DOI: 10.3390/molecules27010080] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/13/2021] [Accepted: 12/16/2021] [Indexed: 11/25/2022] Open
Abstract
Propolis, also known as bee-glue, is a resinous substance produced by honeybees from materials collected from plants they visit. It contains mixtures of wax and bee enzymes and is used by bees as a building material in their hives and by humans for different purposes in traditional healthcare practices. Although the composition of propolis has been shown to depend on its geographic location, climatic zone, and local flora; two largely studied types of propolis: (i) New Zealand and (ii) Brazilian green propolis have been shown to possess Caffeic Acid Phenethyl Ester (CAPE) and Artepillin C (ARC) as the main bioactive constituents, respectively. We have earlier reported that CAPE and ARC possess anticancer activities, mediated by abrogation of mortalin-p53 complex and reactivation of p53 tumor suppressor function. Like CAPE, Artepillin C (ARC) and the supercritical extract of green propolis (GPSE) showed potent anticancer activity. In this study, we recruited low doses of GPSE and ARC (that did not affect either cancer cell proliferation or migration) to investigate their antistress potential using in vitro cell based assays. We report that both GPSE and ARC have the capability to disaggregate metal- and heat-induced aggregated proteins. Metal-induced aggregation of GFP was reduced by fourfold in GPSE- as well as ARC-treated cells. Similarly, whereas heat-induced misfolding of luciferase protein showed 80% loss of activity, the cells treated with either GPSE or ARC showed 60–80% recovery. Furthermore, we demonstrate their pro-hypoxia (marked by the upregulation of HIF-1α) and neuro-differentiation (marked by differentiation morphology and upregulation of expression of GFAP, β-tubulin III, and MAP2). Both GPSE and ARC also offered significant protection against oxidative stress and, hence, may be useful in the treatment of old age-related brain pathologies.
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13
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Radhakrishnan N, Dhanjal JK, Sari AN, Ishida Y, Terao K, Kaul SC, Sundar D, Wadhwa R. Caffeic acid phenethyl ester (CAPE) confers wild type p53 function in p53 Y220C mutant: bioinformatics and experimental evidence. Discov Oncol 2021; 12:64. [PMID: 35201513 PMCID: PMC8777538 DOI: 10.1007/s12672-021-00461-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 12/07/2021] [Indexed: 12/26/2022] Open
Abstract
Mutations in the tumor suppressor protein p53 is a prevalent feature in majority of cancers resulting in inactivation of its activities related to control of cell cycle progression and proliferation. p53Y220C is one of the common hotspot mutations that causes decrease in its thermodynamic stability. Some small molecules have been shown to bind to the mutated site and restore its wild type thermodynamics and tumor suppressor function. In this study, we have explored the potential of caffeic acid phenethyl ester (CAPE-a bioactive compound from propolis) to interact with p53Y220C and restore its wild type p53 (p53wt) transcription activation and tumor suppressor activities. We recruited computational methods, viz. molecular docking, molecular dynamics simulations and free energy calculations to study the interaction of CAPE at the mutation crevice and found that it has potential to restore p53wt function of the p53Y220C mutant similar to a previously described restoration molecule PK7242. We provide cell-based experimental evidence to these predictions and suggest CAPE as a potential natural drug for treatment of p53Y220C mutant harboring cancers.
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Affiliation(s)
- Navaneethan Radhakrishnan
- DAILAB, Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi, 110 016 India
| | - Jaspreet Kaur Dhanjal
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, 305 8565 Japan
- Department of Computational Biology, Indraprastha Institute of Information Technology Delhi, Okhla Industrial Estate, Phase III, New Delhi, 110 020 India
| | - Anissa Nofita Sari
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, 305 8565 Japan
| | - Yoshiyuki Ishida
- Cyclochem Co., Ltd., 7-4-5 Minatojima-minamimachi, Chuo-ku, Kobe, 650 0047 Japan
| | - Keiji Terao
- Cyclochem Co., Ltd., 7-4-5 Minatojima-minamimachi, Chuo-ku, Kobe, 650 0047 Japan
| | - Sunil C. Kaul
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, 305 8565 Japan
| | - Durai Sundar
- DAILAB, Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi, 110 016 India
| | - Renu Wadhwa
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, 305 8565 Japan
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14
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Hou CP, Tsui KH, Chang KS, Sung HC, Hsu SY, Lin YH, Yang PS, Chen CL, Feng TH, Juang HH. Caffeic acid phenethyl ester inhibits the growth of bladder carcinoma cells by upregulating growth differentiation factor 15. Biomed J 2021; 45:763-775. [PMID: 34662721 DOI: 10.1016/j.bj.2021.10.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 09/30/2021] [Accepted: 10/07/2021] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Caffeic acid phenethyl ester (CAPE), a bioactive component of propolis, has beneficial effects on cancer prevention. Growth differentiation factor 15 (GDF15) is an antitumor gene of bladder cancer. Therefore, this study investigated the anti-cancer effect of CAPE on bladder carcinoma cells and related mechanisms. METHODS The expressions of GDF15, N-myc downstream-regulated gene 1 (NDRG1), and maspin, and the activations of ERK, JNK, p38, and AMPKα1/2 in human bladder cells after gene transfection or knockdown were determined by immunoblot, RT-qPCR, and reporter assays. The assays of 5-ethynyl-2'-deoxyuridine (EdU), CyQUANT cell proliferation, and Matrigel invasion, and the xenograft animal study were used to assess the cell proliferation, invasion, and tumorigenesis. RESULTS GDF15 expression in epithelial cells was negatively correlated with neoplasia in vitro. Also, GDF15 exhibits in bladder fibroblasts and smooth muscle cells. CAPE-induced expressions of NDRG1 and maspin decreased cell proliferation and invasion of bladder carcinoma cells in a GDF15-dependent manner in vitro. The xenograft animal study suggesting CAPE attenuated tumor growth in vivo. CAPE increased phosphorylation of ERK, JNK, p38, and AMPKα1/2 to modulate the GDF15 expressions. Pretreatments with ERK, JNK, or p38 inhibitors partially inhibited the CAPE effects on the inductions of GDF15, NDRG1, or maspin. Knockdown of AMPKα1/2 attenuated the CAPE-induced GDF15 expression and cell proliferation in bladder carcinoma cells. CONCLUSIONS Our findings indicate that CAPE is a promising agent for anti-tumor growth in human bladder carcinoma cells via the upregulation of GDF15.
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Affiliation(s)
- Chen-Pang Hou
- Department of Urology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ke-Hung Tsui
- Department of Urology, Shuang Ho Hospital, New Taipei City, Taiwan; Department of Medicine; TMU Research Center of Urology and Kindey, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Kang-Shuo Chang
- Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hsin-Ching Sung
- Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Shu-Yuan Hsu
- Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yu-Hsiang Lin
- Department of Urology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Pei-Shan Yang
- Department of Urology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Chien-Lun Chen
- Department of Urology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Tsui-Hsia Feng
- Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan; School of Nursing, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Horng-Heng Juang
- Department of Urology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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15
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Role of Dietary Antioxidants in p53-Mediated Cancer Chemoprevention and Tumor Suppression. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:9924328. [PMID: 34257824 PMCID: PMC8257365 DOI: 10.1155/2021/9924328] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 05/31/2021] [Indexed: 02/07/2023]
Abstract
Cancer arises through a complex interplay between genetic, behavioral, metabolic, and environmental factors that combined trigger cellular changes that over time promote malignancy. In terms of cancer prevention, behavioral interventions such as diet can promote genetic programs that may facilitate tumor suppression; and one of the key tumor suppressors responsible for initiating such programs is p53. The p53 protein is activated by various cellular events such as DNA damage, hypoxia, heat shock, and overexpression of oncogenes. Due to its role in cell fate decisions after DNA damage, regulatory pathways controlled by p53 help to maintain genome stability and thus “guard the genome” against mutations that cause cancer. Dietary intake of flavonoids, a C15 group of polyphenols, is known to inhibit cancer progression and assist DNA repair through p53-mediated mechanisms in human cells via their antioxidant activities. For example, quercetin arrests human cervical cancer cell growth by blocking the G2/M phase cell cycle and inducing mitochondrial apoptosis through a p53-dependent mechanism. Other polyphenols such as resveratrol upregulate p53 expression in several cancer cell lines by promoting p53 stability, which in colon cancer cells results in the activation of p53-mediated apoptosis. Finally, among vitamins, folic acid seems to play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in patients with premalignant lesions by significantly increased expression of p53. In this review, we discuss the role of these and other dietary antioxidants in p53-mediated cell signaling in relation to cancer chemoprevention and tumor suppression in normal and cancer cells.
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16
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Ghramh HA, Ibrahim EH, Ahmad Z. Antimicrobial, immunomodulatory and cytotoxic activities of green synthesized nanoparticles from Acacia honey and Calotropis procera. Saudi J Biol Sci 2021; 28:3367-3373. [PMID: 34121874 PMCID: PMC8175998 DOI: 10.1016/j.sjbs.2021.02.085] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 02/10/2021] [Accepted: 02/28/2021] [Indexed: 12/11/2022] Open
Abstract
Calotropis procera and Somra (Acacia) honey are used in traditional medicine. The benefits of mixing 20% Somra honey and C. procera leaf water extract (CPLWExt) were aimed to be studied. Honey/CPLWExt were utilized to produce silver nanoparticles (AgNPs) separately. AgNPs were characterized via UV/Vis and electron microscope scanning. Bio-molecules in CPLWExt/honey were investigated utilizing FT-IR spectroscopy. Biological activities of CPLWExt and honey were tested. The outcomes showed that CPLWExt and honey have numerous functional groups and could produce AgNPs. CPLWExt, CPLWExt + AgNPs, honey and honey + AgNPs hindered the growth of rat splenocytes, while CPLWExt + honey invigorated it. Antimicrobial power was found in CPLWExt and honey, which increased in the presence of AgNPs. Honey/honey + AgNPs suppressed the proliferation of HeLa and HepG2 cells. In conclusion, honey/CPLWExt could produce AgNPs and showed immunomodulatory and antibacterial power. Somra honey/honey + AgNPs have anticancer power. Somra honey + CPLWExt reflected a good immunostimulatory powers that can be nominated as an immunostimulant.
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Affiliation(s)
- Hamed A. Ghramh
- Research Center for Advanced Materials Science (RCAMS), King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia
- Unit of Bee Research and Honey Production, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia
- Biology Department, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia
| | - Essam H. Ibrahim
- Research Center for Advanced Materials Science (RCAMS), King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia
- Biology Department, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia
- Blood Products Quality Control and Research Department, National Organization for Research and Control of Biologicals, Cairo 12611, Egypt
| | - Zubair Ahmad
- Research Center for Advanced Materials Science (RCAMS), King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia
- Unit of Bee Research and Honey Production, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia
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17
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Huang Y, Zhou C, Wen H, Chen Y, Xie Y, Lan X, Lin J, Huang X, Mo Y, Yang C, Wang Q, Wang C. Jianpi-Huayu Formula Inhibits Development of Hepatocellular Carcinoma by Regulating Expression of miR-602, Which Targets the RASSF1A Gene. Integr Cancer Ther 2021; 19:1534735419900804. [PMID: 32046536 PMCID: PMC7016307 DOI: 10.1177/1534735419900804] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
The traditional Chinese medicine formula Jianpi-Huayu (JPHY) has been reported to be effective in the treatment of hepatocellular carcinoma (HCC). However, its underlying mechanism remains unclear. In this article, we employed an orthotopic transplantation model in nude mice to explore whether JPHY could inhibit the development of HCC by regulating miR-602, which targets the Ras association domain-containing protein 1A (RASSF1A) pathway. HCC SMMC-7721 cells were treated with JPHY to test whether the RASSF1A gene as mediated by miR-602 affected the proliferation and apoptosis of tumor cells. We subsequently detected miR-602, RASSF1A, and tumor cell apoptosis-related markers in cells and liver tumor tissues. We observed that mice treated with JPHY had smaller tumors and higher survival rates than untreated ones. Similarly, JPHY-treated SMMC-7721 cells exhibited alterations in morphology and higher cytotoxicity compared with the control group. Furthermore, we found that JPHY decreased overexpression of miR-602 and increased protein expression levels of the RASS1A gene, which in turn altered protein expression levels of tumor cell apoptosis-related genes in the cells and liver tumor tissues of drug-treated mice. These results indicated that JPHY could potentially be used to treat HCC by targeting miR-602, which targets the RASSF1A gene, which in turn plays a major role in HCC pathogenesis.
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Affiliation(s)
- Yajing Huang
- Guangzhou University of Chinese Medicine, Guangzhou, China.,Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou, China
| | - Cheng Zhou
- Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou, China.,South China University of Technology, Guangzhou, China
| | - Huihong Wen
- Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, China
| | - Yongxu Chen
- Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China
| | - Yingjie Xie
- Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou, China
| | - Xiaohe Lan
- Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou, China
| | - Juze Lin
- Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou, China
| | - Xuhui Huang
- Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou, China
| | - Yousheng Mo
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Cong Yang
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qi Wang
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Changjun Wang
- Guangzhou University of Chinese Medicine, Guangzhou, China.,Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou, China
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18
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Masadah R, Ikram D, Rauf S. Effects of propolis and its bioactive components on breast cancer cell pathways and the molecular mechanisms involved. Breast Dis 2021; 40:S15-S25. [PMID: 34057114 DOI: 10.3233/bd-219003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Breast cancer is a female malignancy that is a significant cause of mortality worldwide. Currently, investigations on natural ingredients as new candidates for chemopreventive agents and breast cancer chemotherapies are increasing. Propolis is a natural resinous material produced by honeybees that exhibit anticancer potential. Several studies have mentioned the major bioactive compounds of propolis, but their mechanism of action is not clearly understood. OBJECTIVES The purpose of this review is to collect and summarize the evidence related to the effectiveness of propolis and its bioactive contents as candidates for breast cancer therapy and analyze the molecular mechanisms involved in their therapeutic pathways. METHODS We reviewed 94 articles from journals and databases, extracted the results, and produced summaries and conclusions. RESULTS Propolis and its bioactive ingredients show cytotoxic, anti-proliferative, pro-autophagic, anti-metastatic, and antioxidant activities, as well as synergistic effects with chemotherapy or radiotherapy in breast cancer. Its therapeutic activity involves various target molecules, including NF-κβ, Fas receptors, p53, TLR4, ANXA7, and voltage-gated Na+ channel (VGSC). CONCLUSION The bioactive components of propolis and the target molecules involved need to be explored further to develop new breast cancer therapies and overcome the problem of chemoradiation resistance.
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Affiliation(s)
- Rina Masadah
- Department of Pathology Anatomy, Hasanuddin University, Makassar, Indonesia
| | - Dzul Ikram
- Department of Pathology Anatomy, Hasanuddin University, Makassar, Indonesia
- Department of Histology, Muslim University of Indonesia, Makassar, Indonesia
| | - Syahrul Rauf
- Department of Obstetric and Gynecology, Hasanuddin University, Makassar, Indonesia
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19
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Soudi H, Falsafi T, Gharavi S, Mahboubi M. The Role of Helicobacter pylori Proinflammatory Outer Membrane Protein and Propolis in Immunomodulation on U937 Macrophage Cell Model. Galen Med J 2020; 9:e1687. [PMID: 34466568 PMCID: PMC8343919 DOI: 10.31661/gmj.v9i0.1687] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 12/22/2019] [Accepted: 01/24/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Regarding the important role of proinflammatory outer membrane protein (OipA) in the pathogenesis of Helicobacter pylori infection and immunomodulatory activity of propolis, we aimed to evaluate the immunogenicity effect of a purified recombinant OipA protein and propolis in the induction of two cytokines, interferon-gamma (IFN-γ) and interleukin-4 (IL-4), in a macrophage cell model. MATERIALS AND METHODS The recombinant protein used in the present study corresponding to the oipA expressing a 34-35 kDa protein. OipA protein was purified by Ni-NTA affinity chromatography. The purified OipA protein (2.5- 40 μg /mL) and the propolis ethanolic extract (5-40 μg/mL) were incubated with phorbol 12-myristate 13-acetate-treated human myelomonocytic cell line U937 cells. IL-4 and IFN-γ levels were measured after 48 hours of incubation using enzyme-linked immunosorbent assay. RESULTS The amounts of IL-4 and IFN-γ were significantly increased. The optimum concentration of OipA for the secretion of IL-4 was 5 μg/ml (P<0.0001). At higher concentrations, the amount of IL-4 diminished until suppression at 40 μg/mL. The optimum concentration of propolis, resulting in the most significant increased secretion of both IL-4 and IFN-γ was 40 μg/mL (P=0.0001 and P=0.0004). CONCLUSION We found that an OipA concentration of 10 μg/mL was more effective for IFN-γ production; however, it was not effective for the high production of IL-4. Therefore, it is postulated that the OipA could mainly induce a Th1 response through the production of IFN-γ. We also observed propolis's capability to induce IFN-γ production; however, the effective concentration for this was the same as for IL-4. Therefore, as an adjuvant, proper concentration of propolis is required for OipA to give the optimum response.
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Affiliation(s)
- Hengameh Soudi
- Microbiology Department, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Tahereh Falsafi
- Microbiology Department, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Sara Gharavi
- Biotechnology Department, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Mohaddeseh Mahboubi
- Medicinal Plants Research Department, Research and Development, Tabib-Daru Pharmaceutical Company, Kashan, Iran
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20
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Oliveira MTA, de Alencar MVOB, de Paulo Dos Anjos Landim V, Moura GMM, da Cruz JIO, Dos Santos EA, Coutinho HDM, Andrade JC, de Menezes IRA, Ribeiro PRV, de Brito ES, de Sousa EO, Uchoa AF. UPLC-MS-QTOF analysis and antifungal activity of Cumaru ( Amburana cearensis). 3 Biotech 2020; 10:545. [PMID: 33269180 DOI: 10.1007/s13205-020-02551-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 11/09/2020] [Indexed: 11/28/2022] Open
Abstract
This study was aimed at investigating the phytochemical constituents, antifungal properties and antibiotic-modifying activity of the aqueous crude extract and fractions of Amburana cearensis seeds (CEFAC). The CEFAC were chemically characterized by LC-MS/MS-QTOF. In addition, the antifungal activity was assayed by the microdilution method against strains of Candida albicans. The phytochemical profile of CEFAC exhibited phenolic compounds, organic acids, and polyphenols. The results of the assessment of antifungal activity reveled an IC50 ranging from 45.6 to 2048 µg/mL. Interestingly, when CEFAC was associated with Fluconazole, we evidenced a decreased IC50 (1.81-11.9 µg/mL), suggesting a synergism with antibiotic. It was possible to identify in the crude extract and fractions several phenolic compounds, organic acids, and some polyphenols in positive ionization mode. These results suggest that CEFAC may present compounds with the ability to interact and act synergistically with antimicrobial drugs, highlighting its potential as an alternative source for the development of new antimicrobial agents.
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Affiliation(s)
- Maria Tatiana Alves Oliveira
- Laboratory of Chemistry and Function of Bioactive Proteins, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte Brazil
- Department of Biomedical Science, University Centre INTA-UNINTA, Sobral, Ceará Brazil
| | | | | | - Geovanna Maria Medeiros Moura
- Laboratory of Chemistry and Function of Bioactive Proteins, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte Brazil
| | - Joelton Igor Oliveira da Cruz
- Laboratory of Chemistry and Function of Bioactive Proteins, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte Brazil
| | - Elizeu Antunes Dos Santos
- Laboratory of Chemistry and Function of Bioactive Proteins, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte Brazil
| | - Henrique Douglas Melo Coutinho
- Laboratory of Microbiology and Molecular Biology-LMBM, Regional University of Cariri-URCA, Rua Cel. Antonio Luis 1161, Pimenta, Crato, Ceará 63105-000 Brazil
| | - Jacqueline Cosmo Andrade
- Laboratory of Bioassays-LABIO, Educator Training Institute, Federal University of Cariri-UFCA, Campus Brejo Santo, Juazeiro do Norte, Ceará Brazil
| | | | | | - Edy Sousa de Brito
- Multiuser Laboratory of Natural Products Chemistry-LMQPN, Embrapa Agroindustria Tropical, Fortaleza, Ceará Brazil
| | - Erlânio Oliveira de Sousa
- Laboratory of Food Physicochemical Analysis-LAFIQ, Technology College of Cariri-FATEC, Juazeiro do Norte, Ceará Brazil
| | - Adriana Ferreira Uchoa
- Laboratory of Chemistry and Function of Bioactive Proteins, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte Brazil
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21
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Moise AR, Bobiş O. Baccharis dracunculifolia and Dalbergia ecastophyllum, Main Plant Sources for Bioactive Properties in Green and Red Brazilian Propolis. PLANTS (BASEL, SWITZERLAND) 2020; 9:E1619. [PMID: 33233429 PMCID: PMC7700410 DOI: 10.3390/plants9111619] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 11/18/2020] [Accepted: 11/19/2020] [Indexed: 02/06/2023]
Abstract
Nowadays, propolis is used as a highly valuable product in alternative medicine for improving health or treating a large spectrum of pathologies, an ingredient in pharmaceutical products, and also as a food additive. Different vegetal materials are collected by honeybees and mixed with wax and other own substances in order to obtain the final product, called propolis. It is known as the bee product with the widest chemical composition due to the raw material collected by the bees. Different types are known worldwide: green Brazilian propolis (having Baccharis dracunculifolia as the major plant source), red Brazilian propolis (from Dalbergia ecastophyllum), European propolis (Populus nigra L.), Russian propolis (Betula verrucosa Ehrh), Cuban and Venezuelan red propolis (Clusia spp.), etc. An impressive number of scientific papers already demonstrate the pharmacological potential of different types of propolis, the most important activities being the antimicrobial, anti-inflammatory, antitumor, immunomodulatory, and antioxidant activities. However, the bioactive compounds responsible for each activity have not been fully elucidated. This review aims to collect important data about the chemical composition and bioactive properties of the vegetal sources and to compare with the chemical composition of respective propolis types, in order to determine the connection between the floral source and the propolis properties.
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Affiliation(s)
- Adela Ramona Moise
- Department of Apiculture and Sericulture, Faculty of Animal Breeding and Biotechnologies, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania;
| | - Otilia Bobiş
- Life Science Institute “King Michael I of Romania”, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania
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22
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Talebi M, Talebi M, Farkhondeh T, Samarghandian S. Molecular mechanism-based therapeutic properties of honey. Biomed Pharmacother 2020; 130:110590. [PMID: 32768885 DOI: 10.1016/j.biopha.2020.110590] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 07/24/2020] [Accepted: 07/28/2020] [Indexed: 12/14/2022] Open
Abstract
Honey and its phenolic compounds specifically chrysin are focused as nutritional supplements and likewise as valued phytochemicals, nutraceuticals, and phytopharmaceuticals alone, or adjuvant with some conventional medications to cause synergistic therapeutic or cytotoxic effects. Through the verified beneficial strategies combat several disturbances, phenolic compounds play fundamental functions in the avoidance and treatment of disorders. Oxidative stress, inflammation, and apoptosis are the three most imperative physiological reactions in the prevalence of numerous ailments. Honey, chrysin, and other phenolic compounds detected in honey can modify clinical conditions via modulation of these contrivances and correlated signaling pathways. The current study desires to review the therapeutic effects of honey and its allied molecular mechanisms. Evidenced-base studies show that honey would represent therapeutic potential against various types of cancer and tumor proliferation (colorectal cancer, breast cancer, bladder cancer, leukemia, glioma, hepatocellular cancer, pancreatic cancer, and melanoma), wounds, diabetes mellitus, neurological (depression, Parkinson disease, and Alzheimer's disease), respiratory, gastrointestinal (peptic ulcer and ulcerative colitis), cardiovascular disorders, renal injuries, liver diseases and many other kinds of physiological dysfunctionalities through various molecular mechanisms contributed with oxidative stress, inflammatory process, and apoptosis.
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Affiliation(s)
- Marjan Talebi
- Department of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, 19166, Iran
| | - Mohsen Talebi
- Department of Chemistry and Biochemistry, The University of Texas at Arlington, 700 Planetarium Place, Arlington, TX 76019, United States; Food Safety Net Services, San Antonio, TX 78216, United States
| | - Tahereh Farkhondeh
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Saeed Samarghandian
- Healthy Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
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23
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Wang J, Bhargava P, Yu Y, Sari AN, Zhang H, Ishii N, Yan K, Zhang Z, Ishida Y, Terao K, Kaul SC, Miyako E, Wadhwa R. Novel Caffeic Acid Phenethyl Ester-Mortalin Antibody Nanoparticles Offer Enhanced Selective Cytotoxicity to Cancer Cells. Cancers (Basel) 2020; 12:cancers12092370. [PMID: 32825706 PMCID: PMC7564736 DOI: 10.3390/cancers12092370] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 08/01/2020] [Accepted: 08/13/2020] [Indexed: 12/12/2022] Open
Abstract
Caffeic acid phenethyl ester (CAPE) is a key bioactive ingredient of honeybee propolis and is claimed to have anticancer activity. Since mortalin, a hsp70 chaperone, is enriched in a cancerous cell surface, we recruited a unique cell internalizing anti-mortalin antibody (MotAb) to generate mortalin-targeting CAPE nanoparticles (CAPE-MotAb). Biophysical and biomolecular analyses revealed enhanced anticancer activity of CAPE-MotAb both in in vitro and in vivo assays. We demonstrate that CAPE-MotAb cause a stronger dose-dependent growth arrest/apoptosis of cancer cells through the downregulation of Cyclin D1-CDK4, phospho-Rb, PARP-1, and anti-apoptotic protein Bcl2. Concomitantly, a significant increase in the expression of p53, p21WAF1, and caspase cleavage was obtained only in CAPE-MotAb treated cells. We also demonstrate that CAPE-MotAb caused a remarkably enhanced downregulation of proteins critically involved in cell migration. In vivo tumor growth assays for subcutaneous xenografts in nude mice also revealed a significantly enhanced suppression of tumor growth in the treated group suggesting that these novel CAPE-MotAb nanoparticles may serve as a potent anticancer nanomedicine.
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Affiliation(s)
- Jia Wang
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan; (J.W.); (P.B.); (Y.Y.); (A.N.S.); (H.Z.); (N.I.); (K.Y.); (S.C.K.)
- Graduate School of Life & Environmental Sciences, University of Tsukuba, Ibaraki 305-8575, Japan;
| | - Priyanshu Bhargava
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan; (J.W.); (P.B.); (Y.Y.); (A.N.S.); (H.Z.); (N.I.); (K.Y.); (S.C.K.)
| | - Yue Yu
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan; (J.W.); (P.B.); (Y.Y.); (A.N.S.); (H.Z.); (N.I.); (K.Y.); (S.C.K.)
- Biomedical Research Institute (BMRI), National Institute of Advanced Industrial Science & Technology (AIST), Ikeda 563-8577, Japan
| | - Anissa Nofita Sari
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan; (J.W.); (P.B.); (Y.Y.); (A.N.S.); (H.Z.); (N.I.); (K.Y.); (S.C.K.)
| | - Huayue Zhang
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan; (J.W.); (P.B.); (Y.Y.); (A.N.S.); (H.Z.); (N.I.); (K.Y.); (S.C.K.)
| | - Noriyuki Ishii
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan; (J.W.); (P.B.); (Y.Y.); (A.N.S.); (H.Z.); (N.I.); (K.Y.); (S.C.K.)
| | - Kangmin Yan
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan; (J.W.); (P.B.); (Y.Y.); (A.N.S.); (H.Z.); (N.I.); (K.Y.); (S.C.K.)
| | - Zhenya Zhang
- Graduate School of Life & Environmental Sciences, University of Tsukuba, Ibaraki 305-8575, Japan;
| | - Yoshiyuki Ishida
- CycloChem Co., Ltd., 7-4-5 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; (Y.I.); (K.T.)
| | - Keiji Terao
- CycloChem Co., Ltd., 7-4-5 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; (Y.I.); (K.T.)
| | - Sunil C. Kaul
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan; (J.W.); (P.B.); (Y.Y.); (A.N.S.); (H.Z.); (N.I.); (K.Y.); (S.C.K.)
- KAUL-Tech Co. Ltd., 3-24 Nagakunidai, Tsuchiura City, Ibaraki 300-0810, Japan
| | - Eijiro Miyako
- School of Materials Science, Japan Advanced Institute of Science & Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan;
| | - Renu Wadhwa
- AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan; (J.W.); (P.B.); (Y.Y.); (A.N.S.); (H.Z.); (N.I.); (K.Y.); (S.C.K.)
- Correspondence: ; Tel.: +81-29-8-61-9464
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24
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Sari AN, Bhargava P, Dhanjal JK, Putri JF, Radhakrishnan N, Shefrin S, Ishida Y, Terao K, Sundar D, Kaul SC, Wadhwa R. Combination of Withaferin-A and CAPE Provides Superior Anticancer Potency: Bioinformatics and Experimental Evidence to Their Molecular Targets and Mechanism of Action. Cancers (Basel) 2020; 12:E1160. [PMID: 32380701 PMCID: PMC7281427 DOI: 10.3390/cancers12051160] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 04/29/2020] [Accepted: 04/29/2020] [Indexed: 12/12/2022] Open
Abstract
We have earlier reported anticancer activity in Withaferin A (Wi-A), a withanolide derived from Ashwagandha (Withania somnifera) and caffeic acid phenethyl ester (CAPE), an active compound from New Zealand honeybee propolis. Whereas Wi-A was cytotoxic to both cancer and normal cells, CAPE has been shown to cause selective death of cancer cells. In the present study, we investigated the efficacy of Wi-A, CAPE, and their combination to ovarian and cervical cancer cells. Both Wi-A and CAPE were seen to activate tumor suppressor protein p53 by downregulation of mortalin and abrogation of its interactions with p53. Downregulation of mortalin translated to compromised mitochondria integrity and function that affected poly ADP-ribose polymerase1 (PARP1); a key regulator of DNA repair and protein-target for Olaparib, drugs clinically used for treatment of breast, ovarian and cervical cancers)-mediated DNA repair yielding growth arrest or apoptosis. Furthermore, we also compared the docking capability of Wi-A and CAPE to PARP1 and found that both of these could bind to the catalytic domain of PARP1, similar to Olaparib. We provide experimental evidences that (i) Wi-A and CAPE cause inactivation of PARP1-mediated DNA repair leading to accumulation of DNA damage and activation of apoptosis signaling by multiple ways, and (ii) a combination of Wi-A and CAPE offers selective toxicity and better potency to cancer cells.
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Affiliation(s)
- Anissa Nofita Sari
- DAILAB, DBT-AIST International Center for Translational and Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba 305-8565, Japan; (A.N.S.); (P.B.); (J.K.D.); (J.F.P.)
- School of Integrative and Global Majors, University of Tsukuba, Tsukuba 305-8577, Japan
| | - Priyanshu Bhargava
- DAILAB, DBT-AIST International Center for Translational and Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba 305-8565, Japan; (A.N.S.); (P.B.); (J.K.D.); (J.F.P.)
| | - Jaspreet Kaur Dhanjal
- DAILAB, DBT-AIST International Center for Translational and Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba 305-8565, Japan; (A.N.S.); (P.B.); (J.K.D.); (J.F.P.)
- DAILAB, Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi 110 016, India; (N.R.); (S.S.); (D.S.)
| | - Jayarani F. Putri
- DAILAB, DBT-AIST International Center for Translational and Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba 305-8565, Japan; (A.N.S.); (P.B.); (J.K.D.); (J.F.P.)
| | - Navaneethan Radhakrishnan
- DAILAB, Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi 110 016, India; (N.R.); (S.S.); (D.S.)
| | - Seyad Shefrin
- DAILAB, Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi 110 016, India; (N.R.); (S.S.); (D.S.)
| | - Yoshiyuki Ishida
- CycloChem Co. Ltd., 7-4-5 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan; (Y.I.); (K.T.)
| | - Keiji Terao
- CycloChem Co. Ltd., 7-4-5 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan; (Y.I.); (K.T.)
| | - Durai Sundar
- DAILAB, Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi 110 016, India; (N.R.); (S.S.); (D.S.)
| | - Sunil C. Kaul
- DAILAB, DBT-AIST International Center for Translational and Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba 305-8565, Japan; (A.N.S.); (P.B.); (J.K.D.); (J.F.P.)
- School of Integrative and Global Majors, University of Tsukuba, Tsukuba 305-8577, Japan
| | - Renu Wadhwa
- DAILAB, DBT-AIST International Center for Translational and Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba 305-8565, Japan; (A.N.S.); (P.B.); (J.K.D.); (J.F.P.)
- School of Integrative and Global Majors, University of Tsukuba, Tsukuba 305-8577, Japan
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25
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Khan H, Reale M, Ullah H, Sureda A, Tejada S, Wang Y, Zhang ZJ, Xiao J. Anti-cancer effects of polyphenols via targeting p53 signaling pathway: updates and future directions. Biotechnol Adv 2020; 38:107385. [PMID: 31004736 DOI: 10.1016/j.biotechadv.2019.04.007] [Citation(s) in RCA: 95] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 04/14/2019] [Accepted: 04/16/2019] [Indexed: 02/06/2023]
Abstract
The anticancer effects of polyphenols are ascribed to several signaling pathways including the tumor suppressor gene tumor protein 53 (p53). Expression of endogenous p53 is silent in various types of cancers. A number of polyphenols from a wide variety of dietary sources could upregulate p53 expression in several cancer cell lines through distinct mechanisms of action. The aim of this review is to focus the significance of p53 signaling pathways and to provide molecular intuitions of dietary polyphenols in chemoprevention by monitoring p53 expression that have a prominent role in tumor suppression.
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Affiliation(s)
- Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Pakistan..
| | - Marcella Reale
- Department of Medical Oral and Biotechnological Sciences, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Scalo (CH), Italy
| | - Hammad Ullah
- Department of Pharmacy, Abdul Wali Khan University, Pakistan
| | - Antoni Sureda
- Research Group on Community Nutrition and Oxidative Stress and CIBEROBN, Instituto de Salud Carlos III (ISCIII), University of Balearic Islands, Palma de Mallorca, Spain
| | - Silvia Tejada
- Laboratory of Neurophysiology, University of Balearic Islands, Ctra. Valldemossa Km 75, E-07122 Palma de Mallorca, Balearic Islands, Spain
| | - Ying Wang
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Control in Chinese Medicine, University of Macau, Macau
| | - Zhang-Jin Zhang
- School of Chinese Medicine, LKS Faculty of Medicine, University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong.
| | - Jianbo Xiao
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Control in Chinese Medicine, University of Macau, Macau.
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26
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Ghramh HA, Ibrahim EH, Kilany M. Study of anticancer, antimicrobial, immunomodulatory, and silver nanoparticles production by Sidr honey from three different sources. Food Sci Nutr 2020; 8:445-455. [PMID: 31993170 PMCID: PMC6977415 DOI: 10.1002/fsn3.1328] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 10/30/2019] [Accepted: 11/04/2019] [Indexed: 12/20/2022] Open
Abstract
Sidr honey is used as food and medicine in many countries. Study of immunomodulatory and anticancer activity of Sidr honey did not tested before. The aim of this work was to study the anticancer activity and immunomodulatory as well as antimicrobial potential of Sidr honey and its synthesized silver nanoparticles (AgNPs). Sidr honey from three sources (two from Kingdom of Saudi Arabia (KSA) and one from Pakistan) was diluted to 20% and tested for its biological activities and to synthesize AgNPs. The results demonstrated that honeys could produce AgNPs (spherical shape), modulated the growth of normal splenic cells, and have antimicrobial activities. Sidr honey has anticancer activity against HepG2 but not Hela cells. Sidr honey can be used as antimicrobial agent, but can be used as anticancer agent with care as it stimulated cell growth of some lines (e.g., Hala) and inhibited another (e.g., HepG2).
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Affiliation(s)
- Hamed A. Ghramh
- Research Center for Advanced Materials Science (RCAMS)King Khalid UniversityAbhaSaudi Arabia
- Unit of Bee Research and Honey ProductionFaculty of ScienceKing Khalid UniversityAbhaSaudi Arabia
- Biology DepartmentFaculty of Science, King Khalid UniversityAbhaSaudi Arabia
| | - Essam H. Ibrahim
- Research Center for Advanced Materials Science (RCAMS)King Khalid UniversityAbhaSaudi Arabia
- Biology DepartmentFaculty of Science, King Khalid UniversityAbhaSaudi Arabia
- Blood Products Quality Control and Research DepartmentNational Organization for Research and Control of BiologicalsCairoEgypt
| | - Mona Kilany
- Research Center for Advanced Materials Science (RCAMS)King Khalid UniversityAbhaSaudi Arabia
- Department of MicrobiologyNational Organization for Drug Control and Research (NODCAR)GizaEgypt
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27
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Yordanov Y. Caffeic acid phenethyl ester (CAPE): pharmacodynamics and potential for therapeutic application. PHARMACIA 2019. [DOI: 10.3897/pharmacia.66.e38573] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Caffeic acid phenethyl ester (CAPE) is the major pharmacologically-active component of some propolis types, rich in polyphenols, such as poplar propolis types. CAPE has the potential to be applied as a pharmaceutical as it possesses most of the pharmacological activities of propolis, such as anti-proliferative, antioxidant, immunomodulatory, antidiabetic, anti-inflammatory and antimicrobial. Its advantage is that it lacks some of the downsides of total propolis extracts, such as inability for unified standardization, which is cornerstone for implementing its therapeutic potential as a drug. The current paper provides an overview on the pharmacodynamic principles of CAPE. We present literature search outcomes form ClinicalTrials.gov database and from scientific publications, available on Scopus and Crossref databases. We take a round view of CAPE’s potential therapeutic implications in light of approved drugs with related modes of action.
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28
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Ren X, Liu J, Hu L, Liu Q, Wang D, Ning X. Caffeic Acid Phenethyl Ester Inhibits the Proliferation of HEp2 Cells by Regulating Stat3/Plk1 Pathway and Inducing S Phase Arrest. Biol Pharm Bull 2019; 42:1689-1693. [PMID: 31366853 DOI: 10.1248/bpb.b19-00315] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Caffeic acid phenethyl ester (CAPE), an active polyphenolic component of honeybee propolis, has been demonstrated to have many medicinal properties. However, the antitumor effect and mechanism of CAPE on laryngeal carcinoma cells have not been examined. In this study, we treated HEp2 cells with various concentration of CAPE, and the results showed that CAPE can reduce the viability of HEp2 cells with IC50 values of 23.8 ± 0.7 µM for 72 h. Meanwhile, CAPE significantly inhibited activation of signal transducer and activator of transcription (Stat)3 in a concentration dependent manner in HEp2 cells and regulated the expression and transcription of Plk1. AG490, a specific Stat3 inhibitor, not only inhibited the activation and expression of Stat3, but also inhibited the expression of Plk1 in HEp2 cells, so Stat3 was probably involved in the regulation of Plk1 in HEp2 cells. In addition, treatment of CAPE leaded to a blockage of cell cycle in S phase in HEp2 cells. Therefore, CAPE inhibited the proliferation of HEp2 Cells probably by regulating Stat3/Plk1 pathway and inducing S phase arrest.
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Affiliation(s)
- Xiabin Ren
- Department of Otolaryngology, Dahua Hospital
| | - Juan Liu
- Department of Otolaryngology, Eye Ear Nose and Throat Hospital, Fudan University
| | - Li Hu
- Department of Otolaryngology, Eye Ear Nose and Throat Hospital, Fudan University
| | - Quan Liu
- Department of Otolaryngology, Eye Ear Nose and Throat Hospital, Fudan University
| | - Dehui Wang
- Department of Otolaryngology, Eye Ear Nose and Throat Hospital, Fudan University
| | - Xianhui Ning
- Department of Otolaryngology, ZhongShan Hospital, Fudan University
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29
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Rouamba A, Compaoré M, Kiendrebeogo M. Molecular targets of honey bee’s products in cancer prevention and treatment. JOURNAL OF HERBMED PHARMACOLOGY 2019. [DOI: 10.15171/jhp.2019.38] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Chemotherapy and radiotherapy are currently the main treatments for cancer but their toxicities on the surrounding normal cells limit their use in cancer therapy. Moreover, many cancers have developed some resistance to the available anticancer chemicals and put in failure the chemotherapy currently used in the cancer treatment. This failure of the targeted monotherapy resulting from bypass mechanisms has obligated researchers to use agents that interfere with multiple cell-signaling pathways. Recently, researches focused on the use of natural products which can target cancer promoting factors genes expression. Of these natural products, honey has been extensively studied. The pharmacological properties of honey include antioxidant, anti-inflammatory, antibacterial, immunomodulatory, estrogenic and anti-cancer effects. The honey bee’s products are potent sources of nutritional components including sugar, amino-acids, water and minerals. Furthermore honey contains chemopreventive compounds such as flavonoids, phenol acids, tannins, vitamins that may interfere with multiple cell’s pathways and hereby reduce the incidence of many types of cancers. However, the molecular mechanisms of honey bee’s products in cancer prevention and treatment are less known. This review highlights the molecular mechanism of honey bioactive compounds in cancer prevention and treatment.
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Affiliation(s)
- Ablassé Rouamba
- Laboratory of Applied Biochemistry and Chemistry (LABIOCA), UFR-SVT, University Ouaga 1 Pr Joseph KI-ZERBO, 03 BP 7021 Ouagadougou 03, Burkina Faso
| | - Moussa Compaoré
- Laboratory of Applied Biochemistry and Chemistry (LABIOCA), UFR-SVT, University Ouaga 1 Pr Joseph KI-ZERBO, 03 BP 7021 Ouagadougou 03, Burkina Faso
| | - Martin Kiendrebeogo
- Laboratory of Applied Biochemistry and Chemistry (LABIOCA), UFR-SVT, University Ouaga 1 Pr Joseph KI-ZERBO, 03 BP 7021 Ouagadougou 03, Burkina Faso
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30
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Song Y, Guo Q, Gao S, Hua K. miR-454-3p promotes proliferation and induces apoptosis in human cervical cancer cells by targeting TRIM3. Biochem Biophys Res Commun 2019; 516:872-879. [PMID: 31270028 DOI: 10.1016/j.bbrc.2019.06.126] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 06/22/2019] [Indexed: 12/13/2022]
Abstract
Abnormally expressed microRNAs have been demonstrated related to the development and progression of cervical cancer. However, the molecular mechanisms remain largely unkown. Here, we aimed to demonstrate the exact role of miR-454-3p in cervical cancer. Depletion of miR-454-3p in cervical cancer cells resulted in inhibition of cell growth and promotion of cell apoptosis. Bioinformatics analysis predicted that tripartite motif-containing 3 (TRIM3), a tumor suppressor gene in cervical cancer, is a promising target of miR-454-3p. Dual-luciferase reporter gene assay revealed that miR-454-3p directly target TIRM3 by binding to the 3'UTR of TIRM3. In cervical cancer cells (C-33A and SiHa) with endogenous low TRIM3 expression, decreased expression of miR-454-3p significantly elevated TRIM3 expression. In the cervical cancer cell (HeLa) with endogenous high TRIM3 expression, increased expression of miR-454-3p obviously inhibited TRIM3 expression and then manipulating cell growth and apoptosis, down-regulating the expression of P53 and cleaved caspase-3 via P38 MAPK signaling. Taken together, these findings demonstrated miR-454-3p as a cancer promoter by targeting TRIM3 in human cervical cancer.
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Affiliation(s)
- Yu Song
- Medical Center of Diagnosis and Treatment for Cervical Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China
| | - Qisang Guo
- Medical Center of Diagnosis and Treatment for Cervical Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China
| | - Shujun Gao
- Medical Center of Diagnosis and Treatment for Cervical Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.
| | - Keqin Hua
- Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.
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In Search of Panacea-Review of Recent Studies Concerning Nature-Derived Anticancer Agents. Nutrients 2019; 11:nu11061426. [PMID: 31242602 PMCID: PMC6627480 DOI: 10.3390/nu11061426] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 06/18/2019] [Accepted: 06/20/2019] [Indexed: 12/21/2022] Open
Abstract
Cancers are one of the leading causes of deaths affecting millions of people around the world, therefore they are currently a major public health problem. The treatment of cancer is based on surgical resection, radiotherapy, chemotherapy or immunotherapy, much of which is often insufficient and cause serious, burdensome and undesirable side effects. For many years, assorted secondary metabolites derived from plants have been used as antitumor agents. Recently, researchers have discovered a large number of new natural substances which can effectively interfere with cancer cells’ metabolism. The most famous groups of these compounds are topoisomerase and mitotic inhibitors. The aim of the latest research is to characterize natural compounds found in many common foods, especially by means of their abilities to regulate cell cycle, growth and differentiation, as well as epigenetic modulation. In this paper, we focus on a review of recent discoveries regarding nature-derived anticancer agents.
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32
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Gulzar M, Ali S, Khan FI, Khan P, Taneja P, Hassan MI. Binding mechanism of caffeic acid and simvastatin to the integrin linked kinase for therapeutic implications: a comparative docking and MD simulation studies. J Biomol Struct Dyn 2019; 37:4327-4337. [PMID: 30488773 DOI: 10.1080/07391102.2018.1546621] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Integrin linked kinase (ILK) is a Ser/Thr kinase, which regulates various integrin mediated signaling pathways, and is involved in cell adhesion, migration and differentiation. Alteration in the ILK is responsible for abnormal functioning of the cell system, which may lead to the cancer progression and metastasis. Caffeic acid (CA) and simvastatin are used as antioxidant and possess anticancer properties. Thus, inhibiting the kinase activity of ILK by CA and simvastatin may be implicated in the cancer therapy. In this study, we have performed molecular docking followed by 100 ns MD simulations to understand the interaction mechanism of ILK protein with the CA and simvastatin. Average potential energy was found to be highest in case of ILK-CA complex (-770,949 kJ/mol). Binding free energy was found to be higher in case of simvastatin than CA. Our results indicate that simvastatin binds more effectively to the active pocket of ILK. We further performed MTT assay to understand its anticancer potential. Simvastatin shows the IC50 values for HepG2 and MCF-7 as 19.18 ± 0.12 and 13.84 ± 0.22 µM, respectively. However, the IC50 value of CA on HepG2 and MCF-7 was reported as 175.50 ± 1.44 and 144.90 ± 1.53 µM, respectively. Our study provides a deeper insight into the binding mechanism of simvastatin and CA to ILK, which further opens a promising channel for their implications in cancer therapy.
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Affiliation(s)
- Mehak Gulzar
- Department of Biotechnology, Sharda University , Greater Noida , Uttar Pradesh, India
| | - Shahid Ali
- School of Food Science and Engineering, South China University of Technology , Guangzhou , People's Republic of China
| | - Faez Iqbal Khan
- Computational Mechanistic Chemistry and Drug Discovery, Rhodes University , Grahamstown , South Africa
| | - Parvez Khan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia , New Delhi , India
| | - Pankaj Taneja
- Department of Biotechnology, Sharda University , Greater Noida , Uttar Pradesh, India
| | - Md Imtaiyaz Hassan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia , New Delhi , India
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Silva S, Costa EM, Veiga M, Morais RM, Calhau C, Pintado M. Health promoting properties of blueberries: a review. Crit Rev Food Sci Nutr 2018; 60:181-200. [PMID: 30373383 DOI: 10.1080/10408398.2018.1518895] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
With the strengthening of the link between diet and health, several foodstuffs have emerged as possessing potential health benefits such as phenolic rich fruits and vegetables. Blueberries, along with other berries, given their flavonoid and antioxidant content have long since been considered as a particularly interesting health promoting fruit. Therefore, the present work aimed to compile the existing evidences regarding the various potential benefits of blueberry and blueberry based products consumption, giving particular relevance to in vivo works and epidemiological studies whenever available. Overall, the results demonstrate that, while the evidences that support a beneficial role of blueberry and blueberry extracts consumption, further human based studies are still needed.
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Affiliation(s)
- Sara Silva
- CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa/Porto, Porto, Portugal
| | - Eduardo M Costa
- CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa/Porto, Porto, Portugal
| | - Mariana Veiga
- CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa/Porto, Porto, Portugal
| | - Rui M Morais
- CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa/Porto, Porto, Portugal
| | - Conceição Calhau
- Nutrição e Metabolismo, NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.,CINTESIS, Centro de Investigação em Tecnologias e Serviços de Saúde, Universidade do Porto, Portugal
| | - Manuela Pintado
- CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa/Porto, Porto, Portugal
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Chiang KC, Yang SW, Chang KP, Feng TH, Chang KS, Tsui KH, Shin YS, Chen CC, Chao M, Juang HH. Caffeic Acid Phenethyl Ester Induces N-myc Downstream Regulated Gene 1 to Inhibit Cell Proliferation and Invasion of Human Nasopharyngeal Cancer Cells. Int J Mol Sci 2018; 19:ijms19051397. [PMID: 29738439 PMCID: PMC5983775 DOI: 10.3390/ijms19051397] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Revised: 03/27/2018] [Accepted: 04/09/2018] [Indexed: 12/12/2022] Open
Abstract
Caffeic acid phenethyl ester (CAPE), a bioactive component extracted from propolis, is widely studied due to its anti-cancer effect. Nasopharyngeal carcinoma (NPC) is distinct from other head and neck carcinomas and has a high risk of distant metastases. N-myc downstream regulated gene 1 (NDRG1) is demonstrated as a tumor suppressor gene in several cancers. Our result showed that CAPE treatment could repress NPC cell growth, through induction of S phase cell cycle arrest, and invasion. CAPE treatment stimulated NDRG1 expression in NPC cells. NDRG1 knockdown increased NPC cell proliferation and invasion and rendered NPC cells less responsive to CAPE growth-inhibiting effect, indicating CAPE repressed NPC cell growth partly through NDRG1indcution. CAPE treatment increased phosphorylation of ERK, JNK, and p38 in a dose- and time-dependent manner. Pre-treatments by inhibitors of ERK (PD0325901), JNK (SP600125), or p38 (SB201290), respectively, all could partly inhibit the CAPE effect on NDRG1 induction in NPC cells. Further, STAT3 activity was also repressed by CAPE in NPC cells. In summary, CAPE attenuates NPC cell proliferation and invasion by upregulating NDRG1 expression via MAPK pathway and by inhibiting phosphorylation of STAT3. Considering the poor prognosis of NPC patients with metastasis, CAPE could be a promising agent against NPC.
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Affiliation(s)
- Kun-Chun Chiang
- Zebrafish Center, Department of General Surgery, Chang Gung Memorial Hospital, Keelung 204, Taiwan;
| | - Shih-Wei Yang
- Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Keelung 204, Taiwan;
| | - Kai-Ping Chang
- Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital Lin-Kou, Kwei-Shan, Tao-Yuan 204, Taiwan;
| | - Tsui-Hsia Feng
- School of Nursing, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 244, Taiwan;
| | - Kang-Shuo Chang
- Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 244, Taiwan;
| | - Ke-Hung Tsui
- Department of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Tao-Yuan 244, Taiwan;
| | - Yi-Syuan Shin
- Department of Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 244, Taiwan; (Y.-S.S.); (C.-C.C.)
| | - Chiu-Chun Chen
- Department of Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 244, Taiwan; (Y.-S.S.); (C.-C.C.)
| | - Mei Chao
- Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 244, Taiwan;
- Department of Hepato-Gastroenterology, Liver Research Center, Chang Gung Memorial Hospital Lin-Kou, Kwei-Shan, Tao-Yuan 244, Taiwan
| | - Horng-Heng Juang
- Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 244, Taiwan;
- Department of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Tao-Yuan 244, Taiwan;
- Correspondence: ; Tel.: +886-3-2118800; Fax: +886-3-2118112
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Ahmed S, Sulaiman SA, Baig AA, Ibrahim M, Liaqat S, Fatima S, Jabeen S, Shamim N, Othman NH. Honey as a Potential Natural Antioxidant Medicine: An Insight into Its Molecular Mechanisms of Action. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:8367846. [PMID: 29492183 PMCID: PMC5822819 DOI: 10.1155/2018/8367846] [Citation(s) in RCA: 137] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 11/19/2017] [Indexed: 12/13/2022]
Abstract
Honey clasps several medicinal and health effects as a natural food supplement. It has been established as a potential therapeutic antioxidant agent for various biodiverse ailments. Data report that it exhibits strong wound healing, antibacterial, anti-inflammatory, antifungal, antiviral, and antidiabetic effects. It also retains immunomodulatory, estrogenic regulatory, antimutagenic, anticancer, and numerous other vigor effects. Data also show that honey, as a conventional therapy, might be a novel antioxidant to abate many of the diseases directly or indirectly associated with oxidative stress. In this review, these wholesome effects have been thoroughly reviewed to underscore the mode of action of honey exploring various possible mechanisms. Evidence-based research intends that honey acts through a modulatory road of multiple signaling pathways and molecular targets. This road contemplates through various pathways such as induction of caspases in apoptosis; stimulation of TNF-α, IL-1β, IFN-γ, IFNGR1, and p53; inhibition of cell proliferation and cell cycle arrest; inhibition of lipoprotein oxidation, IL-1, IL-10, COX-2, and LOXs; and modulation of other diverse targets. The review highlights the research done as well as the apertures to be investigated. The literature suggests that honey administered alone or as adjuvant therapy might be a potential natural antioxidant medicinal agent warranting further experimental and clinical research.
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Affiliation(s)
- Sarfraz Ahmed
- Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150 Kelantan, Malaysia
- Department of Biochemistry, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Siti Amrah Sulaiman
- Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150 Kelantan, Malaysia
| | - Atif Amin Baig
- Faculty of Medicine, Universiti Sultan Zainal Abidin, Darul Iman, Kuala Terengganu, 20400 Terengganu, Malaysia
| | - Muhammad Ibrahim
- Department of Biochemistry, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Sana Liaqat
- Department of Biochemistry, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Saira Fatima
- Department of Biochemistry, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Sadia Jabeen
- Department of Biochemistry, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Nighat Shamim
- Department of Biochemistry, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Nor Hayati Othman
- Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150 Kelantan, Malaysia
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36
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Yu HJ, Shin JA, Yang IH, Won DH, Ahn CH, Kwon HJ, Lee JS, Cho NP, Kim EC, Yoon HJ, Lee JI, Hong SD, Cho SD. Apoptosis induced by caffeic acid phenethyl ester in human oral cancer cell lines: Involvement of Puma and Bax activation. Arch Oral Biol 2017; 84:94-99. [DOI: 10.1016/j.archoralbio.2017.09.024] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 08/24/2017] [Accepted: 09/24/2017] [Indexed: 02/06/2023]
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37
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Yucel B, Sonmez M. Repression of oxidative phosphorylation sensitizes leukemia cell lines to cytarabine. Hematology 2017; 23:330-336. [DOI: 10.1080/10245332.2017.1402454] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Affiliation(s)
- Burcu Yucel
- Medical Faculty, Department of Medical Biology, Karadeniz Technical University, Trabzon, Turkey
| | - Mehmet Sonmez
- Medical Faculty, Department of Internal Medicine, Division of Hematology, Karadeniz Technical University, Trabzon, Turkey
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38
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Khan SU, Anjum SI, Rahman K, Ansari MJ, Khan WU, Kamal S, Khattak B, Muhammad A, Khan HU. Honey: Single food stuff comprises many drugs. Saudi J Biol Sci 2017; 25:320-325. [PMID: 29472785 PMCID: PMC5815988 DOI: 10.1016/j.sjbs.2017.08.004] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Revised: 07/16/2017] [Accepted: 08/14/2017] [Indexed: 01/22/2023] Open
Abstract
Honey is a natural food item produced by honey bees. Ancient civilizations considered honey as a God gifted prestigious product. Therefore, a huge literature is available regarding honey importance in almost all religions. Physically, honey is a viscous and jelly material having no specific color. Chemically, honey is a complex blend of many organic and inorganic compounds such as sugars, proteins, organic acids, pigments, minerals, and many other elements. Honey use as a therapeutic agent is as old as human civilization itself. Prior to the appearance of present day drugs, honey was conventionally used for treating many diseases. At this instant, the modern research has proven the medicinal importance of honey. It has broad spectrum anti-biotic, anti-viral and anti-fungal activities. Honey prevents and kills microbes through different mechanism such as elevated pH and enzyme activities. Till now, no synthetic compound that works as anti-bacterial, anti-viral and anti-fungal drugs has been reported in honey yet it works against bacteria, viruses and fungi while no anti-protozoal activity has been reported. Potent anti-oxidant, anti-inflammatory and anti-cancerous activities of honey have been reported. Honey is not only significant as anti-inflammatory drug that relieve inflammation but also protect liver by degenerative effects of synthetic anti-inflammatory drugs. This article reviews physico-chemical properties, traditional use of honey as medicine and mechanism of action of honey in the light of modern scientific medicinal knowledge.
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Affiliation(s)
| | - Syed Ishtiaq Anjum
- Department of Zoology, Kohat University of Science and Technology, Kohat 26000, Pakistan
- Corresponding author.
| | - Khaista Rahman
- Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan
| | - Mohammad Javed Ansari
- Department of Plant Protection, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Wasim Ullah Khan
- School of Chemistry and Chemical Engineering, Sun Yat- Sen University, Guangzhou 510275, PR China
| | - Sajid Kamal
- School of Biotechnology, Jiangnan University, Wuxi 214122, PR China
| | - Baharullah Khattak
- Department of Microbiology, Kohat University of Science & Technology, Kohat 26000, Pakistan
| | - Ali Muhammad
- Huazhong Agricultural University, Wuhan 430070, PR China
| | - Hikmat Ullah Khan
- Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan
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Samadi N, Mozaffari-Khosravi H, Rahmanian M, Askarishahi M. Effects of bee propolis supplementation on glycemic control, lipid profile and insulin resistance indices in patients with type 2 diabetes: a randomized, double-blind clinical trial. JOURNAL OF INTEGRATIVE MEDICINE-JIM 2017; 15:124-134. [PMID: 28285617 DOI: 10.1016/s2095-4964(17)60315-7] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Propolis, a natural resinous substance made by bees from material extracted from plants, flowers and bee's wax, has shown great therapeutic effects and been widely used in food and drug industries. Recently, some researchers have studied the effect of this substance in the treatment of diabetes. OBJECTIVE The purpose of this trial was to determine the effect of bee propolis on glycemic control, serum lipid profile and insulin resistance indices in patients with type 2 diabetes (T2D). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS This randomized clinical trial involved 66 patients with T2D, which were randomly divided into two groups of intervention (IG) and placebo (PG). IG received 300 mg three times a day for a total of 900 mg/d of propolis pills, while PG received similar pills, lacking propolis, on the same schedule for 12 weeks. MAIN OUTCOME MEASURES Fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), serum insulin and insulin resistance indices were the main outcome measures. RESULTS The mean change in FBG between the IG ((17.76 ± 27.72) mg/dL decrease) and the PG ((6.48 ± 42.77) mg/dL increase) was significantly different (P = 0.01). Change in mean HbA1c had a similar pattern to FBG. The mean change in TC between the IG ((5.16 ± 43.80) mg/dL increase) and the PG ((28.9 ± 27.4) mg/dL increase) was also significantly different (P = 0.01), showing the protective role of propolis against the increase in TC. The change in mean LDL was similar to mean TC. There was no significant difference in other lipids or insulin resistance indices between the two groups. CONCLUSION Based on this study, the daily intake of 900 mg of bee propolis supplement for 12 weeks results in improvement of glycemic and some serum lipid levels in patients with T2D. TRIAL REGISTRATION This study is registered on the website of Iranian Ministry of Health (www.irct.ir) with proprietary code of IRCT2014080218659N1.
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Affiliation(s)
- Nazli Samadi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hassan Mozaffari-Khosravi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Yazd Diabetic Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Masoud Rahmanian
- Yazd Diabetic Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Department of Internal Medicine, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohsen Askarishahi
- Department of Biostatistics and Epidemiology, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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40
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Substituted Caffeic and Ferulic Acid Phenethyl Esters: Synthesis, Leukotrienes Biosynthesis Inhibition, and Cytotoxic Activity. Molecules 2017; 22:molecules22071124. [PMID: 28684707 PMCID: PMC6152019 DOI: 10.3390/molecules22071124] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 07/04/2017] [Accepted: 07/04/2017] [Indexed: 01/09/2023] Open
Abstract
Glioblastoma multiforme (GBM) is an aggressive brain tumor that correlates with short patient survival and for which therapeutic options are limited. Polyphenolic compounds, including caffeic acid phenethyl ester (CAPE, 1a), have been investigated for their anticancer properties in several types of cancer. To further explore these properties in brain cancer cells, a series of caffeic and ferulic acid esters bearing additional oxygens moieties (OH or OCH3) were designed and synthesized. (CAPE, 1a), but not ferulic acid phenethyl ester (FAPE, 1b), displayed substantial cytotoxicity against two glioma cell lines. Some but not all selected compounds derived from both (CAPE, 1a) and (FAPE, 1b) also displayed cytotoxicity. All CAPE-derived compounds were able to significantly inhibit 5-lipoxygenase (5-LO), however FAPE-derived compounds were largely ineffective 5-LO inhibitors. Molecular docking revealed new hydrogen bonds and π-π interactions between the enzyme and some of the investigated compounds. Overall, this work highlights the relevance of exploring polyphenolic compounds in cancer models and provides additional leads in the development of novel therapeutic strategies in gliomas.
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41
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Chung LC, Chiang KC, Feng TH, Chang KS, Chuang ST, Chen YJ, Tsui KH, Lee JC, Juang HH. Caffeic acid phenethyl ester upregulates N-myc downstream regulated gene 1 via ERK pathway to inhibit human oral cancer cell growth in vitro and in vivo. Mol Nutr Food Res 2017; 61. [PMID: 28181403 DOI: 10.1002/mnfr.201600842] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 01/21/2017] [Accepted: 02/02/2017] [Indexed: 12/12/2022]
Abstract
SCOPE Caffeic acid phenethyl ester (CAPE), a bioactive component of propolis, is considered as a new anti-cancer agent. Oral squamous cell carcinoma (OSCC) is the most common oral cancer with unsatisfying survival. N-myc downstream regulated family genes (NDRGs) involve in numerous physiological processes. We investigated the anti-cancer effect of CAPE on OSCC and related mechanisms. METHODS AND RESULTS Cell proliferation assay, western blot, gene transfection and knockdown, and reporter assay were applied. We showed that CAPE attenuated OSCC cell proliferation and invasion in vitro, and safely and effectively inhibited OSCC cell growth in a xenograft animal model. CAPE treatment induced NDRG1, but not NDRG2 and NDRG3, expression in OSCC cells as determined by western blot, RT-qPCR, and reporter assay. The 5'-deletion assay demonstrated that CAPE increased NDRG1 promoter activity depending on the region of -128 to +46 of the 5'-flanking of NDRG1 gene. NDRG1 gene knockdown attenuated CAPE anti-growth effect on OSCC cells. CAPE activated mitogen-activated protein kinase (MAPK) signaling pathway. The extracellular signal regulated kinase (ERK) inhibitor (PD0325901) and ERK1 knockdown blocked CAPE-induced NDRG1 expression in OSCC cells. CONCLUSION CAPE activated MAPK signaling pathway and increased NDRG1 expression through phosphorylation of ERK1/2 to repress OSCC cells growth.
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Affiliation(s)
- Li-Chuan Chung
- Department of General Education Center, Mackay Medicine, Nursing and Management College, New Taipei City, Taiwan
| | - Kun-Chun Chiang
- Zebrafish Center, Department of General Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Tsui-Hsia Feng
- School of Nursing, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan
| | - Kang-Shuo Chang
- Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan
| | - Sung-Ting Chuang
- Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan
| | - Yu-Jen Chen
- Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan
| | - Ke-Hung Tsui
- Department of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Tao-Yuan, Taiwan
| | - Jehn-Chuan Lee
- Department of Otolaryngology, Mackay Memorial Hospital, Taipei, Taiwan.,School of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Horng-Heng Juang
- Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.,Department of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Tao-Yuan, Taiwan
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Cruz PN, Pereira TC, Guindani C, Oliveira DA, Rossi MJ, Ferreira SR. Antioxidant and antibacterial potential of butia (Butia catarinensis) seed extracts obtained by supercritical fluid extraction. J Supercrit Fluids 2017. [DOI: 10.1016/j.supflu.2016.09.022] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Anantharaju PG, Gowda PC, Vimalambike MG, Madhunapantula SV. An overview on the role of dietary phenolics for the treatment of cancers. Nutr J 2016; 15:99. [PMID: 27903278 PMCID: PMC5131407 DOI: 10.1186/s12937-016-0217-2] [Citation(s) in RCA: 288] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 11/21/2016] [Indexed: 02/07/2023] Open
Abstract
Plant derived phenolic compounds have been shown to inhibit the initiation and progression of cancers by modulating genes regulating key processes such as: (a) oncogenic transformation of normal cells; (b) growth and development of tumors; and (c) angiogenesis and metastasis. Recent studies focusing on identifying the molecular basis of plant phenolics-induced cancer cell death have demonstrated down-regulation of: (a) oncogenic survival kinases such as PI3K and Akt; (b) cell proliferation regulators that include Erk1/2, D-type Cyclins, and Cyclin Dependent Kinases (CDKs); (c) transcription factors such as NF-kβ, NRF2 and STATs; (d) histone deacetylases HDAC1 and HDAC2; and (e) angiogenic factors VEGF, FGFR1 and MIC-1. Furthermore, while inhibiting oncogenic proteins, the phenolic compounds elevate the expression of tumor suppressor proteins p53, PTEN, p21, and p27. In addition, plant phenolic compounds and the herbal extracts rich in phenolic compounds modulate the levels of reactive oxygen species (ROS) in cells thereby regulate cell proliferation, survival and apoptosis. Furthermore, recent studies have demonstrated that phenolic compounds undergo transformation in gut microbiota thereby acquire additional properties that promote their biological activities. In vitro observations, preclinical and epidemiological studies have shown the involvement of plant phenolic acids in retarding the cancer growth. However, to date, there is no clinical trial as such testing the role of plant phenolic compounds for inhibiting tumor growth in humans. More over, several variations in response to phenolic acid rich diets-mediated treatment among individuals have also been reported, raising concerns about whether phenolic acids could be used for treating cancers. Therefore, we have made an attempt to (a) address the key structural features of phenolic acids required for exhibiting potent anti-cancer activity; (b) review the reported findings about the mechanisms of action of phenolic compounds and their transformation by gut microbiota; and (c) update the toxicological aspects and anti-tumor properties of phenolic compounds and extracts containing phenolic compounds in animals.
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Affiliation(s)
- Preethi G Anantharaju
- Department of Biochemistry, Center of Excellence in Molecular Biology and Regenerative Medicine, JSS Medical College, JSS University, Mysore, 570 015, Karnataka, India
| | - Prathima C Gowda
- Department of Pharmacology, JSS Medical College, JSS University, Mysore, 570 015, Karnataka, India
| | | | - SubbaRao V Madhunapantula
- Department of Biochemistry, Center of Excellence in Molecular Biology and Regenerative Medicine, JSS Medical College, JSS University, Mysore, 570 015, Karnataka, India.
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44
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Influence of coffee and its components on breast cancer: A review. ASIAN PACIFIC JOURNAL OF TROPICAL DISEASE 2016. [DOI: 10.1016/s2222-1808(16)61140-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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45
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Wadhwa R, Nigam N, Bhargava P, Dhanjal JK, Goyal S, Grover A, Sundar D, Ishida Y, Terao K, Kaul SC. Molecular Characterization and Enhancement of Anticancer Activity of Caffeic Acid Phenethyl Ester by γ Cyclodextrin. J Cancer 2016; 7:1755-1771. [PMID: 27698914 PMCID: PMC5039358 DOI: 10.7150/jca.15170] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Accepted: 06/29/2016] [Indexed: 01/05/2023] Open
Abstract
Caffeic Acid Phenethyl Ester (CAPE) is a key component in New Zealand propolis, known for a variety of health promoting and therapeutic potentials. We investigated the molecular mechanism of anticancer and anti-metastasis activities of CAPE. cDNA array performed on the control and CAPE-treated breast cancer cells revealed activation of DNA damage signaling involving upregulation of GADD45α and p53 tumor suppressor proteins. Molecular docking analysis revealed that CAPE is capable of disrupting mortalin-p53 complexes. We provide experimental evidence and demonstrate that CAPE induced disruption of mortalin-p53 complexes led to nuclear translocation and activation of p53 resulting in growth arrest in cancer cells. Furthermore, CAPE-treated cells exhibited downregulation of mortalin and several other key regulators of cell migration accountable for its anti-metastasis activity. Of note, we found that whereas CAPE was unstable in the culture medium (as it gets degraded into caffeic acid by secreted esterases), its complex with gamma cyclodextrin (γCD) showed high efficacy in anti-tumor and anti-metastasis assays in vitro and in vivo (when administered through either intraperitoneal or oral route). The data proposes that CAPE-γCD complex is a potent anti-cancer and anti-metastasis reagent.
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Affiliation(s)
- Renu Wadhwa
- DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), National Institute of Advanced Industrial Science & Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba - 305 8565, Japan
| | - Nupur Nigam
- DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), National Institute of Advanced Industrial Science & Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba - 305 8565, Japan;; Graduate School of Life & Environmental Sciences, University of Tsukuba, Ibaraki - 305 8575, Japan
| | - Priyanshu Bhargava
- DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), National Institute of Advanced Industrial Science & Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba - 305 8565, Japan;; Graduate School of Life & Environmental Sciences, University of Tsukuba, Ibaraki - 305 8575, Japan
| | - Jaspreet Kaur Dhanjal
- Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology Delhi, New Delhi - 110 016, India
| | - Sukriti Goyal
- School of Biotechnology, Jawaharlal Nehru University, New Delhi - 110 067, India
| | - Abhinav Grover
- School of Biotechnology, Jawaharlal Nehru University, New Delhi - 110 067, India
| | - Durai Sundar
- Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology Delhi, New Delhi - 110 016, India
| | - Yoshiyuki Ishida
- CycloChem Co., Ltd., 7-4-5 Minatojima-minamimachi, Chuo-ku, Kobe - 650 0047, Japan
| | - Keiji Terao
- CycloChem Co., Ltd., 7-4-5 Minatojima-minamimachi, Chuo-ku, Kobe - 650 0047, Japan;; Graduate School of Medicine, Kobe University, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe - 650 0017, Japan
| | - Sunil C Kaul
- DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), National Institute of Advanced Industrial Science & Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba - 305 8565, Japan
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46
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Sforcin JM. Biological Properties and Therapeutic Applications of Propolis. Phytother Res 2016; 30:894-905. [DOI: 10.1002/ptr.5605] [Citation(s) in RCA: 259] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Revised: 01/18/2016] [Accepted: 02/15/2016] [Indexed: 01/06/2023]
Affiliation(s)
- José M. Sforcin
- Department of Microbiology and Immunology; Institute of Biosciences of Botucatu, UNESP; 18618-970 Botucatu SP Brazil
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Erdemli HK, Akyol S, Armutcu F, Gulec MA, Canbal M, Akyol O. Melatonin and caffeic acid phenethyl ester in the regulation of mitochondrial function and apoptosis: The basis for future medical approaches. Life Sci 2016; 148:305-12. [DOI: 10.1016/j.lfs.2016.01.026] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2015] [Revised: 01/12/2016] [Accepted: 01/13/2016] [Indexed: 12/20/2022]
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A preliminary study of apoptosis induction in glioma cells via alteration of the Bax/Bcl-2-p53 axis by transformed and non-transformed root extracts of Leonurus sibiricus L. Tumour Biol 2016; 37:8753-64. [PMID: 26743778 DOI: 10.1007/s13277-015-4714-2] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 12/20/2015] [Indexed: 12/15/2022] Open
Abstract
Leonurus sibiricus L. is a traditional medicinal plant which occurs in southern Siberia, China, Korea, Japan, and Vietnam. The plant shows several pharmacological effects, but the most interesting is its anti-cancer activity. The aim of our study was to examine the induction of apoptosis in malignant glioma cells, the most aggressive primary brain tumors of the central nervous system, following treatment with transformed root (TR) or non-transformed root (NR) L. sibiricus extracts. Both the NR and TR extracts were found to have cytotoxic activity in the glioma primary cells. The human glioblastoma cell lines obtained from patients were confirmed to be tumorogenic by the following three markers: D10S1709, D10S1172, and D22S283. HPLC and MS analysis revealed the presence of polyphenolic compounds (chlorogenic acid, ferulic acid, caffeic acid, p-coumaric acid, ellagic acid, and verbascoside) in both sets of root extracts. In summary, our findings demonstrate that treatment of the glioma cells with NR and TR extracts resulted (a) in significant cell growth inhibition, (b) S- and G2/M-phase cell cycle arrest, and (c) apoptosis in a dose-dependent fashion by changing Bax/Bcl-2 ratio (about 4-fold increase) and p53 (5-fold increase) activation. These findings indicate that NR and TR extracts exhibit anti-cancer activity through the regulation of genes involved in apoptosis. This is the first report to demonstrate the cytotoxic effect of polyphenolic extracts from L. sibiricus roots against glioma cells, but further studies are required to understand the complete mechanism of its apoptosic activity.
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Demir S, Aliyazicioglu Y, Turan I, Misir S, Mentese A, Yaman SO, Akbulut K, Kilinc K, Deger O. Antiproliferative and proapoptotic activity of Turkish propolis on human lung cancer cell line. Nutr Cancer 2015; 68:165-72. [PMID: 26700423 DOI: 10.1080/01635581.2016.1115096] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Cancer is a heterogeneous disease, two of whose characteristic features are uncontrollable cell proliferation and insufficient apoptosis. Various studies have investigated the antiproliferative effects of propolis, a natural bee product, from different countries, and its cytotoxic effects have been attributed to its polyphenol contents. The purpose of this study was to show the cytotoxic effects, and possible mechanisms involved, of ethanolic extract of Turkish propolis (EEP) on the human lung cancer (A549) cell line. Cytotoxic activity of EEP on A549 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic action of EEP on A549 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, endoplasmic reticulum stress using RT-PCR, and caspase activity using luminometric analysis. EEP exhibited selective toxicity against A549 cells compared to normal fibroblast cells. We determined that EEP arrested the cell cycle of A549 cells at the G1 phase, induced endoplasmic reticulum stress, caspase activity, and apoptosis and reduced mitochondrial membrane potential. These results indicate that Turkish propolis is capable of reducing cancer cell proliferation and may have a promising role to play in the development of new anticancer drugs in the future.
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Affiliation(s)
- Selim Demir
- a Department of Medical Biochemistry , Institute of Health Sciences, Karadeniz Technical University , Trabzon , Turkey
| | - Yuksel Aliyazicioglu
- b Department of Medical Biochemistry , Faculty of Medicine, Karadeniz Technical University , Trabzon , Turkey
| | - Ibrahim Turan
- c Department of Genetic and Bioengineering , Faculty of Engineering and Natural Sciences, Gumushane University, Gumushane, Turkey, and Medicinal Plants, Traditional Medicine Practice and Research Center, Gumushane University , Gumushane , Turkey
| | - Sema Misir
- d Department of Medical Biochemistry , Institute of Health Sciences, Karadeniz Technical University, Trabzon, Turkey and Department of Biochemistry, Faculty of Pharmacy, Cumhuriyet University , Sivas , Turkey
| | - Ahmet Mentese
- b Department of Medical Biochemistry , Faculty of Medicine, Karadeniz Technical University , Trabzon , Turkey
| | - Serap Ozer Yaman
- a Department of Medical Biochemistry , Institute of Health Sciences, Karadeniz Technical University , Trabzon , Turkey
| | - Kubra Akbulut
- a Department of Medical Biochemistry , Institute of Health Sciences, Karadeniz Technical University , Trabzon , Turkey
| | - Kagan Kilinc
- e Department of Genetic and Bioengineering , Faculty of Engineering and Natural Sciences, Gumushane University , Gumushane , Turkey
| | - Orhan Deger
- b Department of Medical Biochemistry , Faculty of Medicine, Karadeniz Technical University , Trabzon , Turkey
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50
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CAPE Analogs Induce Growth Arrest and Apoptosis in Breast Cancer Cells. Molecules 2015; 20:12576-89. [PMID: 26184141 PMCID: PMC6332101 DOI: 10.3390/molecules200712576] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 07/04/2015] [Accepted: 07/07/2015] [Indexed: 01/24/2023] Open
Abstract
Breast cancer is the second leading cause of death amongst women worldwide. As a result, many have turned their attention to new alternative approaches to treat this disease. Caffeic acid phenylethyl ester (CAPE), a well-known active compound from bee propolis, has been previously identified as a strong antioxidant, anti-inflammatory, antiviral and anticancer molecule. In fact, CAPE is well documented as inducing cell death by inhibiting NFκB and by inducing pro-apoptotic pathways (i.e., p53). With the objective of developing stronger anticancer compounds, we studied 18 recently described CAPE derivatives for their ability to induce apoptosis in breast cancer cell lines. Five of the said compounds, including CAPE, were selected and subsequently characterised for their anticancer mechanism of action. We validated that CAPE is a potent inducer of caspase-dependent apoptosis. Interestingly, some newly synthesized CAPE derivatives also showed greater cell death activity than the lead CAPE structure. Similarly to CAPE, analog compounds elicited p53 activation. Interestingly, one compound in particular, analog 10, induced apoptosis in a p53-mutated cell line. These results suggest that our new CAPE analog compounds may display the capacity to induce breast cancer apoptosis in a p53-dependent and/or independent manner. These CAPE analogs could thus provide new therapeutic approaches for patients with varying genotypic signatures (such as p53 mutations) in a more specific and targeted fashion.
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