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Hasibuan PAZ, Keliat JM, Lubis MF, Nasution A. The ethyl acetate extract of Vernonia amygdalina leaf ameliorates gemcitabine effect against migration and invasion of PANC-1 cells via down-regulation the VEGF, COX 2, and RAS/MEK pathways. Saudi Pharm J 2024; 32:101872. [PMID: 38111670 PMCID: PMC10727942 DOI: 10.1016/j.jsps.2023.101872] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 11/12/2023] [Indexed: 12/20/2023] Open
Abstract
Individuals diagnosed with cancer often turn to the use of herbal remedies with the intention of treating and ameliorating the condition, impeding the progression of metastasis, enhancing immune function, mitigating stress, and inducing relaxation. Recently, medicinal plants were combined with conventional chemotherapy to decrease the side effects and increase the effectiveness of chemotherapy. This study showed the effectiveness of gemcitabine (Gem) was significantly increased after being used together with ethyl acetate extract obtained from Vernonia amygdalina (Eav) leaves. The combination doses of Eav and Gem were determined based on cytotoxic activity using the MTT assay method. The anticancer effect of this combination was identified by several parameters including the apoptosis effect, anti-migration, and anti-invasion activities of PANC-1 cells. Furthermore, this effect was explained via protein expression evaluation using immunohistochemical and flow cytometry. The Eav has a better Inhibitory Concentration 50 (IC50) than Gem of 21.19 ± 0.64 µg/mL and 164.78 ± 1.40 µg/mL. The combination of Eav and Gem at IC50 (1:1) has the strongest activity than Eav and Gem alone at 500.00 µg/mL. The anti-cancer effect of this combination showed significantly increased levels of apoptosis, particularly in the early phase of 17.46 ± 0.35 % (p < 0.0001) than Eav and Gem alone of 7.76 ± 0.25 % and 7.06 ± 0.20 %. A similar impact was evaluated in the migration and invasion of PANC-1 cells after the combination treatment. The % relative migration and cell invasion were significantly decreased compared to the control group and Eav or Gem alone by 21.49 ± 0.96 % and 125.25 ± 5.25 cells, respectively (p < 0.0001). This study found that signature molecules of VEGF, COX2, RAS, and MEK were down-regulated after treatment. Our study suggested that the Eav ameliorates the Gem effect against PANC-1 cells through apoptosis, migration, and invasion influence via RAS/MEK pathways.
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Affiliation(s)
| | - Jane Melita Keliat
- Department of Pharmaceutical and Food Analysis, Faculty of Vocational, Universitas Sumatera Utara, Indonesia
| | - Muhammad Fauzan Lubis
- Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Sumatera Utara, Indonesia
| | - Annisa Nasution
- Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Indonesia
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Samankul A, Senawong G, Utaiwat S, Prompipak J, Woranam K, Phaosiri C, Sripa B, Senawong T. Tiliacora triandra Leaf Powder Ethanolic Extract in Combination with Cisplatin or Gemcitabine Synergistically Inhibits the Growth of Cholangiocarcinoma Cells In Vitro and in Nude Mouse Xenograft Models. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1269. [PMID: 37512080 PMCID: PMC10386122 DOI: 10.3390/medicina59071269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 07/03/2023] [Accepted: 07/05/2023] [Indexed: 07/30/2023]
Abstract
Background and Objectives: The treatments of cholangiocarcinoma (CCA) with Cisplatin (Cis) and Gemcitabine (Gem) often cause side effects and drug resistance. This study aimed to investigate the combined effects of Tiliacora triandra leaf powder ethanolic extract (TLPE) and Cis or Gem on CCA cells in vitro and in nude mouse xenografts. Materials and Methods: Antiproliferative activity was evaluated using MTT assay. Drug interaction was studied by Chou-Talalay method. Apoptosis induction and cell cycle arrest were analyzed by flow cytometry. Cell cycle and apoptosis regulating proteins were evaluated by western blot analysis. Results:Treatments with Cis or Gem in combination with TLPE significantly inhibited the growth of KKU-M213B and KKU-100 cells compared with single drug treatments. Synergistic drug interactions were observed with the dose reduction of Cis and Gem treatments. The safety of TLPE was demonstrated in vitro by the hemolytic assay. Synergistic combination treatments down-regulated Bcl2 and reduced the ratio of Bcl2/Bax in both CCA cells. TLPE enhanced tumor suppression of both Cis and Gem in nude mouse xenograft models. Combination treatments with Cis and TLPE reduced Cis toxicity, as demonstrated by the enhanced body weight change of the treated mice compared with the treatment with Cis alone. Furthermore, TLPE reduced hepatotoxicity caused by Gem treatment and reduced kidney and spleen toxicities caused by Cis treatment. Conclusion: These findings suggest that TLPE enhances the anticancer activity of Cis and Gem and reduces their toxicity both in vitro and in nude mouse xenograft models.
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Affiliation(s)
- Arunta Samankul
- Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Gulsiri Senawong
- Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Suppawit Utaiwat
- Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Jeerati Prompipak
- Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Khanutsanan Woranam
- Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Chanokbhorn Phaosiri
- Department of Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Banchob Sripa
- WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Tropical Disease Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Thanaset Senawong
- Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand
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Ekeuku SO, Etim EP, Pang KL, Chin KY, Mai CW. Vitamin E in the management of pancreatic cancer: A scoping review. World J Gastrointest Oncol 2023; 15:943-958. [PMID: 37389119 PMCID: PMC10302993 DOI: 10.4251/wjgo.v15.i6.943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 02/03/2023] [Accepted: 04/07/2023] [Indexed: 06/14/2023] Open
Abstract
Pancreatic cancer is the leading cause of cancer mortality worldwide. Research investigating effective management strategies for pancreatic cancer is ongoing. Vitamin E, consisting of both tocopherol and tocotrienol, has demonstrated debatable effects on pancreatic cancer cells. Therefore, this scoping review aims to summarize the effects of vitamin E on pancreatic cancer. In October 2022, a literature search was conducted using PubMed and Scopus since their inception. Original studies on the effects of vitamin E on pancreatic cancer, including cell cultures, animal models and human clinical trials, were considered for this review. The literature search found 75 articles on this topic, but only 24 articles met the inclusion criteria. The available evidence showed that vitamin E modulated proliferation, cell death, angiogenesis, metastasis and inflammation in pancreatic cancer cells. However, the safety and bioavailability concerns remain to be answered with more extensive preclinical and clinical studies. More in-depth analysis is necessary to investigate further the role of vitamin E in the management of pancreatic cancers.
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Affiliation(s)
- Sophia Ogechi Ekeuku
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Effiong Paul Etim
- Faculty of Applied Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
| | - Kok-Lun Pang
- Newcastle University Medicine Malaysia, Iskandar Puteri 79200, Johor, Malaysia
| | - Kok-Yong Chin
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
- State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Chun-Wai Mai
- State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
- Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
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Islam R, Yan MP, Yen KP, Rasol NE, Meng CK, Wai LK. Synthesis and biological evaluation of chromone derivatives against triple-negative breast cancer cells. Med Chem Res 2023. [DOI: 10.1007/s00044-023-03048-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2023]
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Mesas C, Quiñonero F, Doello K, Revueltas JL, Perazzoli G, Cabeza L, Prados J, Melguizo C. Active Biomolecules from Vegetable Extracts with Antitumoral Activity against Pancreas Cancer: A Systematic Review (2011-2021). Life (Basel) 2022; 12:1765. [PMID: 36362920 PMCID: PMC9695035 DOI: 10.3390/life12111765] [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] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/20/2022] [Accepted: 10/31/2022] [Indexed: 08/30/2023] Open
Abstract
The emergence of resistance to pancreatic cancer (PC) current treatment requires the development of new therapeutic strategies. In this context, bioactive molecules from plant extracts have shown excellent properties to improve classical therapy against this type of tumor. This systematic review aims to collect all the in vitro studies related to the antiproliferative activity of isolated plant molecules that support their applicability in PC. A total of 620 articles published in the last 10 years were identified, although only 28 were finally included to meet the inclusion criteria. Our results reflect the most important biomolecules from natural compounds that induce cell death in PC and their essential mechanism of cell death, including apoptosis, pathways activated by the KRAS mutation and cycle cell arrest, among others. These in vitro studies provide an excellent molecule guide showing applications against PC and that should be tested in vivo and in clinical trials to determine their usefulness to reduce PC incidence and to improve the prognosis of these patients. However, natural compounds are isolated in small amounts, which prevents comprehensive drug screening, being necessary the role of organic synthesis for the total synthesis of natural compounds or for the synthesis of their simplified and bioactive analogs.
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Affiliation(s)
- Cristina Mesas
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Instituto Biosanitario de Granada (ibs. GRANADA), 18014 Granada, Spain
| | - Francisco Quiñonero
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Instituto Biosanitario de Granada (ibs. GRANADA), 18014 Granada, Spain
| | - Kevin Doello
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Instituto Biosanitario de Granada (ibs. GRANADA), 18014 Granada, Spain
- Medical Oncology Service, Virgen de las Nieves Hospital, 18016 Granada, Spain
| | - José L. Revueltas
- Radiodiagnosis Service, Reina Sofía University Hospital, 14004 Córdoba, Spain
| | - Gloria Perazzoli
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Instituto Biosanitario de Granada (ibs. GRANADA), 18014 Granada, Spain
| | - Laura Cabeza
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Instituto Biosanitario de Granada (ibs. GRANADA), 18014 Granada, Spain
| | - Jose Prados
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Instituto Biosanitario de Granada (ibs. GRANADA), 18014 Granada, Spain
| | - Consolación Melguizo
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Instituto Biosanitario de Granada (ibs. GRANADA), 18014 Granada, Spain
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Ismail NZ, Md Saad S, Adebayo IA, Md Toha Z, Abas R, Mohamad Zain NN, Arsad H. The antiproliferative and apoptotic potential of Clinacanthus nutans against human breast cancer cells through targeted apoptosis pathway. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:81685-81702. [PMID: 35737268 DOI: 10.1007/s11356-022-20858-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 05/12/2022] [Indexed: 06/15/2023]
Abstract
Clinacanthus nutans dichloromethane fraction (CN-Dcm) extract has previously been proven to suppress breast cancer (MCF7) cell proliferation. Despite this, the extrinsic and intrinsic apoptosis mechanisms involved in C. nutans extract-treated MCF7 cells are still unknown. This study was intended to subfractionate CN-Dcm extract using column chromatography and analyse the treated MCF7 cells using the CellTiter 96® AQueous One Solution Cell Proliferation (MTS) assay, Annexin V/propidium iodide (PI) assay, western blot, and reverse transcription-qualitative polymerase chain reaction (RT-qPCR). Out of nine subfraction extracts (SF1 to SF9), SF2 extract strongly inhibited MCF7 cells with the lowest IC50 value (23.51 ± 1.00 µg/mL) and substantially induced apoptosis in the MCF7 cells. In treated MCF7 cells, SF2 extract significantly upregulated the expression of P53, BAX, BID, caspase-8, caspase-9, and caspase-3, while downregulating the expression of BCL2. The presence of potential bioactive chemical compounds in the SF2 extract was identified using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Thus, the SF2 extract has the potential to induce apoptosis in MCF7 cells through intrinsic and extrinsic pathways.
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Affiliation(s)
- Noor Zafirah Ismail
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200, Penang, Kepala Batas, Malaysia
| | - Salwani Md Saad
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200, Penang, Kepala Batas, Malaysia
| | - Ismail Abiola Adebayo
- Department of Clinical Biology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda
- Analystical Biochemistry Research Centre, Universiti Sains Malaysia, Penang, Malaysia
- Microbiology and Immunology Department, School of Biomedical Sciences, Kampala International University, Western Campus, P.O. Box 71, Ishaka-Bushenyi, Uganda
| | - Zaleha Md Toha
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200, Penang, Kepala Batas, Malaysia
| | - Rafedah Abas
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200, Penang, Kepala Batas, Malaysia
| | - Nur Nadhirah Mohamad Zain
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200, Penang, Kepala Batas, Malaysia
| | - Hasni Arsad
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200, Penang, Kepala Batas, Malaysia.
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Gupta S, Kumar A, Tejavath KK. A pharmacognostic approach for mitigating pancreatic cancer: emphasis on herbal extracts and phytoconstituents. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2021. [DOI: 10.1186/s43094-021-00246-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Abstract
Background
Pancreatic cancer is studied as one of the most lethal cancers with currently no control of its lethality, mainly due to its late diagnosis and lack of foolproof treatment processes. Despite continuous efforts being made in looking for therapies to deal with cancer, it keeps on being a labyrinth for the researchers. Efforts like discovering new treatment options, repurposing existing drugs, are continuously made to deal with this cancer.
Main body
With the urge to get answers and the fact that nature has all roots of therapeutics, efforts are made in the direction of finding those answers for providing ministrations for pancreatic cancer from plant products. Plant products are used as treatment options either directly in the form of extracts or an alternative to them is individual phytochemicals that are either isolated from the plants or are commercially synthesized for various purposes. In this review, we put forward such pharmacognostic initiatives made in combating pancreatic cancer, focusing mainly on plant extracts and various phytochemicals; along with the mechanisms which they triggered to fulfill the need for cytotoxicity to pancreatic cancer cells (in vitro and in vivo).
Conclusion
This study will thus provide insights into new combination therapy that can be used and also give a clue on which plant product and phytoconstituent can be used in dealing with pancreatic cancer.
Graphical abstract
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Kim A, Ha J, Kim J, Cho Y, Ahn J, Cheon C, Kim SH, Ko SG, Kim B. Natural Products for Pancreatic Cancer Treatment: From Traditional Medicine to Modern Drug Discovery. Nutrients 2021; 13:nu13113801. [PMID: 34836055 PMCID: PMC8625071 DOI: 10.3390/nu13113801] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 10/20/2021] [Accepted: 10/21/2021] [Indexed: 02/07/2023] Open
Abstract
Pancreatic cancer, the seventh most lethal cancer around the world, is considered complicated cancer due to poor prognosis and difficulty in treatment. Despite all the conventional treatments, including surgical therapy and chemotherapy, the mortality rate is still high. Therefore, the possibility of using natural products for pancreatic cancer is increasing. In this study, 68 natural products that have anti-pancreatic cancer effects reported within five years were reviewed. The mechanisms of anti-cancer effects were divided into four types: apoptosis, anti-metastasis, anti-angiogenesis, and anti-resistance. Most of the studies were conducted for natural products that induce apoptosis in pancreatic cancer. Among them, plant extracts such as Eucalyptus microcorys account for the major portion. Some natural products, including Moringa, Coix seed, etc., showed multi-functional properties. Natural products could be beneficial candidates for treating pancreatic cancer.
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Affiliation(s)
- Ahyeon Kim
- College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea; (A.K.); (J.H.); (J.K.)
| | - Jiwon Ha
- College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea; (A.K.); (J.H.); (J.K.)
| | - Jeongeun Kim
- College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea; (A.K.); (J.H.); (J.K.)
| | - Yongmin Cho
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea; (Y.C.); (J.A.); (S.-H.K.)
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea; (C.C.); (S.-G.K.)
| | - Jimyung Ahn
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea; (Y.C.); (J.A.); (S.-H.K.)
| | - Chunhoo Cheon
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea; (C.C.); (S.-G.K.)
| | - Sung-Hoon Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea; (Y.C.); (J.A.); (S.-H.K.)
| | - Seong-Gyu Ko
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea; (C.C.); (S.-G.K.)
| | - Bonglee Kim
- College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea; (A.K.); (J.H.); (J.K.)
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea; (Y.C.); (J.A.); (S.-H.K.)
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea; (C.C.); (S.-G.K.)
- Correspondence: ; Tel.: +82-2-961-9217
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Xu W, Li J, Li D, Tan J, Ma H, Mu Y, Wen Y, Gan L, Huang X, Li L. Chemical characterization, antiproliferative and antifungal activities of Clinacanthus nutans. Fitoterapia 2021; 155:105061. [PMID: 34673146 DOI: 10.1016/j.fitote.2021.105061] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/29/2021] [Accepted: 10/09/2021] [Indexed: 11/26/2022]
Abstract
Clinacanthus nutans Lindau (Family: Acanthaceae) is a medicinal herb widely distributed in the tropic and subtropic areas of Asia. C. nutans is traditionally consumed as vegetable or herbal tea, as well as a folk medicine for anticancer and antifungal activities. However, to date, chemical constituent responsible for observed health beneficial effects of this medicinal plant is not clear. In the current study, 32 compounds (1-32), including three new megastigmanes (1-3) were isolated from the aerial parts of C. nutans. Their structures were elucidated on the basis of comprehensive NMR, MS, and CD spectroscopic data analysis, as well as chemical hydrolysis. Among the isolates, cycloartane triterpenoids (9, 10, and 12) displayed moderate anti-proliferative effects against HepG2 cell growth with IC50 values ranging from 9.12 to 19.89 μM. Data obtained from flow cytometry analysis and western blotting assays revealed that compounds 9 and 12 induced apoptosis of HepG2 cells by modulating the expression of proteins associated to mitochondrial-mediated apoptotic pathway. Furthermore, megastigmanes 1, 2, 7, and 8 enhanced the anti-Candida albicans activity of amphotericin B (AmB), supporting the synergistic effects between megastigmanes and AmB. This is the first report of anticancer and antifungal potential of cycloartane triterpenoids and megastigmanes in C. nutans, which shed useful insights on the relationship between C. nutans's chemical constituent and its beneficial effects to health. Findings from this study support further development of this medicinal plant for potential pharmaceutical applications.
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Affiliation(s)
- Wen Xu
- Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China
| | - Jiaying Li
- Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China
| | - Dongli Li
- School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China.
| | - Junfeng Tan
- Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China
| | - Hang Ma
- School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, United States
| | - Yu Mu
- Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China
| | - Yan Wen
- School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China
| | - Lishe Gan
- School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China
| | - Xueshi Huang
- Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China.
| | - Liya Li
- Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China.
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Nordin FJ, Pearanpan L, Chan KM, Kumolosasi E, Yong YK, Shaari K, Rajab NF. Immunomodulatory potential of Clinacanthus nutans extracts in the co-culture of triple-negative breast cancer cells, MDA-MB-231, and THP-1 macrophages. PLoS One 2021; 16:e0256012. [PMID: 34379689 PMCID: PMC8357171 DOI: 10.1371/journal.pone.0256012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 07/28/2021] [Indexed: 12/12/2022] Open
Abstract
Triple-negative breast cancer is the main type of breast carcinoma that causes mortality among women because of the limited treatment options and high recurrence. Chronic inflammation has been linked with the tumor microenvironment (TME) in breast cancer progression. Clinacanthus nutans (CN) has gained much attention because of its anticancer properties, but its mechanism remains unclear. We aimed to study the qualitative phytochemical content and elucidate the cytotoxicity effects of CN on human triple-negative breast cancer (TNBC), MDA-MB-231 and human macrophage-like cells such as THP-1 by using sulforhodamine B (SRB) assay. As highly metastatic cells, MDA-MB-231 cells can migrate to the distal position, the effect of CN on migration were also elucidated using the scratch assay. The CN effects on ameliorating chronic inflammation in TME were studied following the co-culture of MDA-MB-231/THP-1 macrophages. The cytokine expression levels of IL-6, IL-1β and tumor necrosis factor-alpha (TNF-α) were determined using ELISA assays. The results showed that both ethanolic and aqueous CN extracts contained alkaloid, phenol and tannin, flavonoid, terpenoid, glycoside and steroid. However, saponin was only found in the aqueous extract of CN. CN was not cytotoxic to both MDA-MB-231 and THP-1 cells. The ability of MDA-MB-231 to migrate was also not halted by CN treatment. However, CN ethanol extract decreased IL-6 at 25 μg/mL (p = 0.02) and 100 μg/mL (p = 0.03) but CN aqueous extract increased IL-6 expression at 50 μg/mL (p = 0.08) and 100 μg/mL (p = 0.02). IL-1β showed decreased expression after treated with CN ethanol and CN aqueous both at 25 μg/mL (p = 0.03). TNF-α were significantly decreased after CN ethanol treatment at concentration 25- (p = 0.001), 50- (p = 0.000) and 100 μg/mL (p = 0.000). CN aqueous extract slightly inhibited TNF-α at all 25–50- and 100 μg/mL (p = 0.001, p = 0.000, p = 0.000, respectively). Overall, CN acts by ameliorating the pro-inflammatory condition in the TME and may be a potential strategy for its anticancer mechanism on highly metastatic breast cancer condition. The major pathways that link both cancer and inflammation were NF-κB and STATs thus further study on the upstream and downstream pathways is needed to fully understand the mechanism of CN extracts in cooling the inflamed TME in breast cancer.
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Affiliation(s)
- Fariza Juliana Nordin
- Biomedical Science Program, Center for Healthy Aging and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Lishantini Pearanpan
- Biomedical Science Program, Center for Healthy Aging and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Kok Meng Chan
- Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Endang Kumolosasi
- Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Yoke Keong Yong
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang, Seri Kembangan, Selangor, Malaysia
| | - Khozirah Shaari
- Faculty of Science, Universiti Putra Malaysia, UPM Serdang, Seri Kembangan, Malaysia
| | - Nor Fadilah Rajab
- Biomedical Science Program, Center for Healthy Aging and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
- * E-mail:
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Recent Advancement in Anticancer Activity of Clinacanthus nutans (Burm. f.) Lindau. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:5560502. [PMID: 34135980 PMCID: PMC8175158 DOI: 10.1155/2021/5560502] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 05/15/2021] [Indexed: 01/17/2023]
Abstract
Clinacanthus nutans is a traditional medicinal herb that is applied for the therapy of snake bites, skin infection, herpes infection, burns, scalds, dysentery, and diabetes. Clinacanthus nutans is also used to treat several cancers, including breast, cervical, colon, gastric, head and neck, liver, lung, pancreatic, and skin cancers, as well as lymphoma and leukemia; however, the underlying mechanisms of its anticancer activity remained undetermined. We searched PubMed and Google with key words “Clinacanthus nutans and cancer” and collected recent papers of Clinacanthus nutans with anticancer activity. We focused on the preparation, effects, and action mechanisms of Clinacanthus nutans extracts on various types of cancers. We hope that this mini review can help update our knowledge about active components, effects, and molecular mechanisms of extracts from this promising herb Clinacanthus nutans for ongoing studies and speed up its clinical application in the future.
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Widjaja SS, Rusdiana, Ichwan M. Enhanced cytotoxic effects of Clinacanthus nutans and doxorubicin in combination toward breast cancer cell lines. J Adv Pharm Technol Res 2021; 12:152-156. [PMID: 34159146 PMCID: PMC8177153 DOI: 10.4103/japtr.japtr_251_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 01/19/2021] [Accepted: 02/24/2021] [Indexed: 12/24/2022] Open
Abstract
Breast cancer is one of the most common cancers with a relatively high mortality rate. Despite the advancement of its medical treatments, many patients are still seeking complementary alternative medicines, namely Clinacanthus nutans which is found mainly in South-East Asian countries. We aim to find the antioxidant properties and cytotoxic activity of the plant extract toward breast cancer cell lines Michigan Cancer Foundation-7 (MCF7) and T47D individually and in combination with doxorubicin. Extractions of C. nutans with ethanol, n-hexane, and ethyl acetate were done using rotatory vacuum evaporators with the reflux method. Screening of biochemical properties was conducted. Antioxidant activity was measured toward α, α-diphenyl-β-picrylhydrazyl (DPPH) with IC50 scores were shown to be highest in ethyl acetate extract. Cytotoxic effects of all three extracts were shown to be low in both MCF7 and T47D cells. However, combinations of 125 μg/ml n-hexane extract of C. nutans, and 0.1 μg/ml doxorubicin in T47D cancer cells showed further proliferation reduction compared to the single administration. The results suggested possible synergisms of the treatment combination.
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Affiliation(s)
- Sry Suryani Widjaja
- Department of Biochemistry, Medical Faculty Universitas Sumatera Utara, Indonesia
| | - Rusdiana
- Department of Biochemistry, Medical Faculty Universitas Sumatera Utara, Indonesia
| | - M Ichwan
- Department of Pharmacology, Medical Faculty Universitas Sumatera Utara, Indonesia
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AlAli M, Alqubaisy M, Aljaafari MN, AlAli AO, Baqais L, Molouki A, Abushelaibi A, Lai KS, Lim SHE. Nutraceuticals: Transformation of Conventional Foods into Health Promoters/Disease Preventers and Safety Considerations. Molecules 2021; 26:molecules26092540. [PMID: 33925346 PMCID: PMC8123587 DOI: 10.3390/molecules26092540] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 03/24/2021] [Accepted: 03/27/2021] [Indexed: 11/27/2022] Open
Abstract
Nutraceuticals are essential food constituents that provide nutritional benefits as well as medicinal effects. The benefits of these foods are due to the presence of active compounds such as carotenoids, collagen hydrolysate, and dietary fibers. Nutraceuticals have been found to positively affect cardiovascular and immune system health and have a role in infection and cancer prevention. Nutraceuticals can be categorized into different classes based on their nature and mode of action. In this review, different classifications of nutraceuticals and their potential therapeutic activity, such as anti-cancer, antioxidant, anti-inflammatory and anti-lipid activity in disease will be reviewed. Moreover, the different mechanisms of action of these products, applications, and safety upon consumers including current trends and future prospect of nutraceuticals will be included.
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Affiliation(s)
- Mudhi AlAli
- Health Sciences Division, Abu Dhabi Women’s College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates; (M.A.); (M.A.); (M.N.A.); (A.O.A.); (L.B.); (K.-S.L.)
| | - Maream Alqubaisy
- Health Sciences Division, Abu Dhabi Women’s College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates; (M.A.); (M.A.); (M.N.A.); (A.O.A.); (L.B.); (K.-S.L.)
| | - Mariam Nasser Aljaafari
- Health Sciences Division, Abu Dhabi Women’s College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates; (M.A.); (M.A.); (M.N.A.); (A.O.A.); (L.B.); (K.-S.L.)
| | - Asma Obaid AlAli
- Health Sciences Division, Abu Dhabi Women’s College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates; (M.A.); (M.A.); (M.N.A.); (A.O.A.); (L.B.); (K.-S.L.)
| | - Laila Baqais
- Health Sciences Division, Abu Dhabi Women’s College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates; (M.A.); (M.A.); (M.N.A.); (A.O.A.); (L.B.); (K.-S.L.)
| | - Aidin Molouki
- Department of Avian Disease Research and Diagnostic, Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization (AREEO), Karaj 31585-854, Iran;
| | - Aisha Abushelaibi
- Dubai Colleges, Higher Colleges of Technology, Dubai 16062, United Arab Emirates;
| | - Kok-Song Lai
- Health Sciences Division, Abu Dhabi Women’s College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates; (M.A.); (M.A.); (M.N.A.); (A.O.A.); (L.B.); (K.-S.L.)
| | - Swee-Hua Erin Lim
- Health Sciences Division, Abu Dhabi Women’s College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates; (M.A.); (M.A.); (M.N.A.); (A.O.A.); (L.B.); (K.-S.L.)
- Correspondence: or ; Tel.: +971-56-389-3757
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Maniam G, Mai CW, Zulkefeli M, Fu JY. Co-encapsulation of gemcitabine and tocotrienols in nanovesicles enhanced efficacy in pancreatic cancer. Nanomedicine (Lond) 2021; 16:373-389. [PMID: 33543651 DOI: 10.2217/nnm-2020-0374] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 01/06/2021] [Indexed: 02/08/2023] Open
Abstract
Aim: To synthesize niosomes co-encapsulating gemcitabine (GEM) and tocotrienols, and physicochemically characterize and evaluate the antipancreatic effects of the nanoformulation on Panc 10.05, SW 1990, AsPC-1 and BxPC-3 cells. Materials & methods: Niosomes-entrapping GEM and tocotrienols composed of Span 60, cholesterol and D-α-tocopheryl polyethylene glycol 1000 succinate were produced by Handjani-Vila and film hydration methods. Results: The film hydration produced vesicles measuring 161.9 ± 0.5 nm, approximately 50% smaller in size than Handjani-Vila method, with maximum entrapment efficiencies of 20.07 ± 0.22% for GEM and 34.52 ± 0.10% for tocotrienols. In Panc 10.05 cells, GEM's antiproliferative effect was enhanced 2.78-fold in combination with tocotrienols. Niosomes produced a significant ninefold enhancement in cytotoxicity of the combination, supported by significantly higher cellular uptake of GEM in the cells. Conclusion: This study is a proof of concept on the synthesis of dual-drug niosomes and their efficacy on pancreatic cancer cells in vitro.
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Affiliation(s)
- Geetha Maniam
- School of Postgraduate Study, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia
- Product Development & Advisory Services Division, Malaysian Palm Oil Board, Bandar Baru Bangi, Selangor, Malaysia
| | - Chun-Wai Mai
- Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia
- Centre for Cancer & Stem Cells Research, Institute for Research, Development & Innovation, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia
| | - Mohd Zulkefeli
- Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia
| | - Ju-Yen Fu
- Product Development & Advisory Services Division, Malaysian Palm Oil Board, Bandar Baru Bangi, Selangor, Malaysia
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Zou C, Yang H, Cui L, Cao X, Huang H, Chen T. Potential hazardous effects of printing room PM2.5 exposure include promotion of lung inflammation and subsequent injury. Mol Med Rep 2020; 22:3213-3224. [PMID: 32945461 PMCID: PMC7453667 DOI: 10.3892/mmr.2020.11399] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Accepted: 06/26/2020] [Indexed: 11/09/2022] Open
Abstract
There have been few studies investigating the potential effects of indoor sources of particulate matter on human health. In this study, the effect of different concentrations of fine particulate matter (PM2.5) collected from a printing room on lung health was examined using cultured cells and a mouse model. Further, the mechanism of lung injury was examined. The results indicated that PM2.5 significantly enhanced malondialdehyde activity (P<0.05), decreased superoxide dismutase activity (P<0.05), upregulated the expression of pro-inflammatory factors including interleukin (IL)-1β, tumor necrosis factor-, IL-6 and downregulated the expression of the inflammatory factor IL-2 (P<0.05). Western blot analysis indicated that PM2.5 significantly enhanced expression of phosphorylated (p)-ERK relative to total ERK, cyclooxygenase-2, p-anti-nuclear-factor-κB (p-NF-κB) relative to NF-κB, transforming growth factor-β1 and Bax relative to Bcl-2 in inflammation (P<0.05), fibrosis and apoptosis signaling pathways. Furthermore, the results revealed that exposure was associated with an increased abundance of pathogens including Burkholderiales, Coriobacteriia, and Betaproteobacteria in in the lungs. In conclusion, exposure to PM2.5 from a printing room significantly increased inflammation, fibrosis, apoptosis and the abundance of pathogenic bacteria, indicating that exposure is potential threat to individuals who spend a significant amount of time in printing rooms.
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Affiliation(s)
- Changwei Zou
- School of Resources Environmental and Chemical Engineering, Key Laboratory of Poyang Lake Environment and Resource Utilization, Ministry of Education, Nanchang University, Nanchang, Jiangxi 330031, P.R. China
| | - Hong Yang
- School of Resources Environmental and Chemical Engineering, Key Laboratory of Poyang Lake Environment and Resource Utilization, Ministry of Education, Nanchang University, Nanchang, Jiangxi 330031, P.R. China
| | - Lanyue Cui
- Nanchang University Queen Mary School, Nanchang, Jiangxi 330031, P.R. China
| | - Xinyi Cao
- Nanchang University Queen Mary School, Nanchang, Jiangxi 330031, P.R. China
| | - Hong Huang
- School of Resources Environmental and Chemical Engineering, Key Laboratory of Poyang Lake Environment and Resource Utilization, Ministry of Education, Nanchang University, Nanchang, Jiangxi 330031, P.R. China
| | - Tingtao Chen
- National Engineering Research Center for Bioengineering Drugs and The Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330031, P.R. China
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Looi CK, Hii LW, Ngai SC, Leong CO, Mai CW. The Role of Ras-Associated Protein 1 (Rap1) in Cancer: Bad Actor or Good Player? Biomedicines 2020; 8:334. [PMID: 32906721 PMCID: PMC7555474 DOI: 10.3390/biomedicines8090334] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 09/02/2020] [Accepted: 09/05/2020] [Indexed: 02/05/2023] Open
Abstract
Metastasis is known as the most life-threatening event in cancer patients. In principle, the immune system can prevent tumor development. However, dysfunctional T cells may fail to eliminate the tumor cells effectively and provide additional survival advantages for tumor proliferation and metastasis. Constitutive activation of Ras-associated protein1 (Rap1) has not only led to T cell anergy, but also inhibited autophagy and supported cancer progression through various oncogenic events. Inhibition of Rap1 activity with its negative regulator, Rap1GAP, impairs tumor progression. However, active Rap1 reduces tumor invasion in some cancers, indicating that the pleiotropic effects of Rap1 signaling in cancers could be cancer-specific. All in all, targeting Rap1 signaling and its regulators could potentially control carcinogenesis, metastasis, chemoresistance and immune evasion. Rap1GAP could be a promising therapeutic target in combating cancer.
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Affiliation(s)
- Chin-King Looi
- School of Postgraduate Study, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia; (C.-K.L.); (L.-W.H.)
| | - Ling-Wei Hii
- School of Postgraduate Study, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia; (C.-K.L.); (L.-W.H.)
- School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia;
| | - Siew Ching Ngai
- School of Biosciences, Faculty of Science and Engineering, University of Nottingham Malaysia, Semenyih, Selangor 43500, Malaysia;
| | - Chee-Onn Leong
- School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia;
- Centre for Cancer and Stem Cells Research, Institute for Research, Development, and Innovation (IRDI), International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia
| | - Chun-Wai Mai
- School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia;
- Centre for Cancer and Stem Cells Research, Institute for Research, Development, and Innovation (IRDI), International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia
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Gan LL, Hii LW, Wong SF, Leong CO, Mai CW. Molecular Mechanisms and Potential Therapeutic Reversal of Pancreatic Cancer-Induced Immune Evasion. Cancers (Basel) 2020; 12:1872. [PMID: 32664564 PMCID: PMC7408947 DOI: 10.3390/cancers12071872] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 07/06/2020] [Accepted: 07/09/2020] [Indexed: 02/05/2023] Open
Abstract
Pancreatic cancer ranks high among the causes of cancer-related mortality. The prognosis of this grim condition has not improved significantly over the past 50 years, despite advancement in imaging techniques, cancer genetics and treatment modalities. Due to the relative difficulty in the early detection of pancreatic tumors, as low as 20% of patients are eligible for potentially curative surgery; moreover, chemotherapy and radiotherapy (RT) do not confer a great benefit in the overall survival of the patients. Currently, emerging developments in immunotherapy have yet to bring a significant clinical advantage among pancreatic cancer patients. In fact, pancreatic tumor-driven immune evasion possesses one of the greatest challenges leading to immunotherapeutic resistance. Most of the immune escape pathways are innate, while poor priming of hosts' immune response and immunoediting constitute the adaptive immunosuppressive machinery. In this review, we extensively discuss the pathway perturbations undermining the anti-tumor immunity specific to pancreatic cancer. We also explore feasible up-and-coming therapeutic strategies that may restore immunity and address therapeutic resistance, bringing hope to eliminate the status quo in pancreatic cancer prognosis.
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Affiliation(s)
- Li-Lian Gan
- School of Postgraduate Study, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia; (L.-L.G.); (L.-W.H.)
| | - Ling-Wei Hii
- School of Postgraduate Study, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia; (L.-L.G.); (L.-W.H.)
- School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia;
| | - Shew-Fung Wong
- School of Medicine, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia;
- Centre for Environmental and Population Health, Institute for Research, Development and Innovation (IRDI), International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia
| | - Chee-Onn Leong
- School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia;
- Centre for Cancer and Stem Cells Research, Institute for Research, Development and Innovation (IRDI), International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia
| | - Chun-Wai Mai
- School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia;
- Centre for Cancer and Stem Cells Research, Institute for Research, Development and Innovation (IRDI), International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia
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Tan NP, Yang SK, Leo TK, Mai CW, Chin SY, Lamasudin D, Lim SHE, Lai KS. Protein expression patterns in hek-Blue™ - Cells treated with Clinacanthus nutans extracts. Pharmacogn Mag 2020. [DOI: 10.4103/pm.pm_281_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Sachdeva T, Low ML, Mai C, Cheong SL, Liew YK, Milton MD. Design, Synthesis and Characterisation of Novel Phenothiazine‐Based Triazolopyridine Derivatives: Evaluation of Anti‐Breast Cancer Activity on Human Breast Carcinoma. ChemistrySelect 2019; 4:12701-12707. [DOI: 10.1002/slct.201903203] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 10/25/2019] [Indexed: 02/05/2023]
Abstract
AbstractA series of novel phenothiazine based [1,2,4]triazolo[4, 3‐a]pyridine scaffolds were designed and synthesized in good yields by the oxidative cyclisation of phenothiazine pyridylhydrazones. Biological responses of all compounds toward a panel of human breast cancer cells (MDA‐MB‐231, MDA‐MB‐468, MCF7, SKBR3 and T47D) and human non‐tumorigenic epithelial breast cells (MCF10 A) were evaluated. Structure‐activity relationship revealed that compound with pendant phenyl ring on phenothiazine exhibited significant cytotoxic activity and apoptotic induction effects against breast cancer cell line with IC50 value 10.2 to 17.6 μM. Notably, the cytotoxic effect was 3.5 fold higher on cancer than non‐cancer cells, indicating potential control of breast cancer with lower side effects. Molecular docking studies confirmed the presence of hydrophobic contacts between appended phenyl ring, triazolopyridine and phenothiazine moieties with adjacent residues within the binding pocket of tubulin. One of the nitrogen in the triazolo ring also showed hydrogen bonding with tubulin. These tubulin interactions were also found with the taxane ring of paclitaxel. Cell cycle analysis confirmed the G2/M arrest induced by this compound on human breast cancer cells. Therefore, the potential anti‐cancer, pro‐apoptotic, and cell cycle arrest warrant further development of this molecule as a new class of anticancer agent.
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Affiliation(s)
| | - May Lee Low
- Department of Pharmaceutical Chemistry School of Pharmacy International Medical University, No. 126 Jalan Jalil Perkasa 19, Bukit Jalil 57000 Kuala Lumpur Malaysia
| | - Chun‐Wai Mai
- Department of Pharmaceutical Chemistry School of Pharmacy International Medical University, No. 126 Jalan Jalil Perkasa 19, Bukit Jalil 57000 Kuala Lumpur Malaysia
- Center for Cancer and Stem Cell Research Institute for Research, Development and Innovation International Medical University, No. 126 Jalan Jalil Perkasa 19, Bukit Jalil 57000 Kuala Lumpur Malaysia
| | - Siew Lee Cheong
- Department of Pharmaceutical Chemistry School of Pharmacy International Medical University, No. 126 Jalan Jalil Perkasa 19, Bukit Jalil 57000 Kuala Lumpur Malaysia
| | - Yun Khoon Liew
- Department of Life Sciences School of Pharmacy International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil 57000 Kuala Lumpur Malaysia
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