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SHINOHARA Y, ELBADAWY M, LIU Y, YAMANAKA M, YAMAMOTO H, SATO Y, AUGOMAA A, ISHIHARA Y, USUI T, SASAKI K. Anticancer potentials of chaga and notoginseng against dog bladder cancer organoids. J Vet Med Sci 2025; 87:232-240. [PMID: 39756955 PMCID: PMC11830434 DOI: 10.1292/jvms.24-0258] [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: 07/07/2024] [Accepted: 12/20/2024] [Indexed: 01/07/2025] Open
Abstract
Muscle-invasive bladder cancer (MIBC) is a common form of BC in dogs. Adjuvant chemotherapy administration is commonly applied in MIBC cases, but patients sometimes experience treatment failure and recurrence. Therefore, supplements with anticancer properties, such as traditional Chinese medicines (TCMs), are required, and they have been widely used in Japanese human medicine and may be useful in veterinary medicine. Furthermore, organoid cultures can mimic the characteristics of their original tissues, such as self-renewal and organization. We previously established a novel experimental model for MIBC using a dog BC organoid (DBCO) culture. Herein, we examined the antiproliferative effects and mechanisms of 39 substances, consisting of TCMs, TCM supplements, and crude drug extracts, on DBCOs. Among the TCMs, D3 (also known as Shibe-ria), which is a mixture of chaga (Inonotus obliquus) and notoginseng (Panax notoginseng), significantly diminished the cell viability of DBCOs. The expression of BC stem cell markers, CD44 and SOX2, was reduced considerably in the D3-treated DBCOs. Among the components of D3, chaga exerted an antiproliferative effect on DBCO, whereas notoginseng did not. The administration of D3 also significantly reduced the volume of DBCO xenografted tumors in mice in vivo. Overall, D3 may have benefits as a natural anticancer supplement in veterinary medicine.
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Affiliation(s)
- Yuta SHINOHARA
- Laboratory of Veterinary Pharmacology, Department of
Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and
Technology, Tokyo, Japan
- Pet Health & Food Division, Iskra Industry Co., Ltd.,
Tokyo, Japan
| | - Mohamed ELBADAWY
- Laboratory of Veterinary Pharmacology, Department of
Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and
Technology, Tokyo, Japan
- Department of Pharmacology, Faculty of Veterinary Medicine,
Benha University, Elqaliobiya, Egypt
- Department of Pathology, College of Veterinary Medicine,
University of Georgia, Athens, GA, USA
| | - Yishan LIU
- Laboratory of Veterinary Pharmacology, Department of
Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and
Technology, Tokyo, Japan
| | - Megumi YAMANAKA
- Laboratory of Veterinary Pharmacology, Department of
Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and
Technology, Tokyo, Japan
| | - Haru YAMAMOTO
- Laboratory of Veterinary Pharmacology, Department of
Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and
Technology, Tokyo, Japan
| | - Yomogi SATO
- Laboratory of Veterinary Pharmacology, Department of
Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and
Technology, Tokyo, Japan
| | - Amira AUGOMAA
- Laboratory of Veterinary Pharmacology, Department of
Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and
Technology, Tokyo, Japan
- Faculty of Veterinary Medicine, Mansoura University,
Mansoura, Egypt
| | | | - Tatsuya USUI
- Laboratory of Veterinary Pharmacology, Department of
Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and
Technology, Tokyo, Japan
| | - Kazuaki SASAKI
- Laboratory of Veterinary Pharmacology, Department of
Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and
Technology, Tokyo, Japan
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Wang J, Beghelli D, Amici A, Sut S, Dall’Acqua S, Lupidi G, Dal Ben D, Bistoni O, Tomassoni D, Belletti B, Musa S, Mahajna J, Pucciarelli S, Marchini C. Chaga Mushroom Triterpenoids Inhibit Dihydrofolate Reductase and Act Synergistically with Conventional Therapies in Breast Cancer. Biomolecules 2024; 14:1454. [PMID: 39595631 PMCID: PMC11591880 DOI: 10.3390/biom14111454] [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: 08/28/2024] [Revised: 10/22/2024] [Accepted: 11/08/2024] [Indexed: 11/28/2024] Open
Abstract
Inonotus obliquus (Chaga) is a medicinal mushroom with several pharmacological properties that is used as a tea in traditional Chinese medicine. In this study, Chaga water extract was digested in vitro to mimic the natural processing and absorption of its biocomponents when it is consumed as functional beverage, and its anticancer activities were evaluated in breast cancer (BC) cell lines, representing HER2-positive and triple-negative subtypes. After chemical characterization by liquid chromatography/mass spectrometry (HR-QTOF) analysis, the effect of Chaga biocomponents on cell viability and cell cycle progression was assessed by MTT assay, FACS analysis, and Western blot. Dihydrofolate reductase (DHFR) activity was measured by an enzymatic assay. Four highly bioactive triterpenoids (inotodiol, trametenolic acid, 3-hydroxy-lanosta-8,24-dien-21-al, and betulin) were identified as the main components, able to decrease BC cell viability and block the cell cycle in G0/G1 by inducing the downregulation of cyclin D1, CDK4, cyclin E, and phosphorylated retinoblastoma protein. DHFR was identified as their crucial target. Moreover, bioactive Chaga components exerted a synergistic action with cisplatin and with trastuzumab in SK-BR-3 cells by inhibiting both HER2 and HER1 activation and displayed an immunomodulatory effect. Thus, Inonotus obliquus represents a source of triterpenoids that are effective against aggressive BC subtypes and display properties of targeted drugs.
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Affiliation(s)
- Junbiao Wang
- School of Biosciences and Veterinary Medicine, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy; (D.B.); (A.A.); (D.T.); (C.M.)
| | - Daniela Beghelli
- School of Biosciences and Veterinary Medicine, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy; (D.B.); (A.A.); (D.T.); (C.M.)
| | - Augusto Amici
- School of Biosciences and Veterinary Medicine, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy; (D.B.); (A.A.); (D.T.); (C.M.)
| | - Stefania Sut
- DAFNAE Dipartimento di Agronomia, Animali, Alimenti, Risorse Naturali e Ambiente, University of Padova, 35020 Legnaro, Italy;
| | - Stefano Dall’Acqua
- DSF Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35121 Padova, Italy;
| | - Giulio Lupidi
- School of Pharmacy, University of Camerino, 62032 Camerino, Italy;
| | - Diego Dal Ben
- School of Pharmacy-Chemistry Interdisciplinary Project (CHIP), University of Camerino, 62032 Camerino, Italy;
| | - Onelia Bistoni
- Rheumatology Unit, Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy;
| | - Daniele Tomassoni
- School of Biosciences and Veterinary Medicine, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy; (D.B.); (A.A.); (D.T.); (C.M.)
| | - Barbara Belletti
- Molecular Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano, Italy;
| | - Sanaa Musa
- Natural Compounds and Organic Synthesis, Migal-Galilee Research Institute, Kiryat Shmona 11016, Israel; (S.M.); (J.M.)
- Department of Biotechnology, Tel Hai College, Kiryat Shmona 1220800, Israel
| | - Jamal Mahajna
- Natural Compounds and Organic Synthesis, Migal-Galilee Research Institute, Kiryat Shmona 11016, Israel; (S.M.); (J.M.)
- Cancer Drug Discovery Program, Migal, Galilee Research Institute, P.O. Box 831, Kiryat Shmona 11016, Israel
| | - Stefania Pucciarelli
- School of Biosciences and Veterinary Medicine, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy; (D.B.); (A.A.); (D.T.); (C.M.)
| | - Cristina Marchini
- School of Biosciences and Veterinary Medicine, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy; (D.B.); (A.A.); (D.T.); (C.M.)
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Arast Y, Esfandiari H, Kamranfar F, Mousavi Z, Ameri Shah Reza M, Pourahmad J. Evaluating the concentration dependent dual effects of β-Glucan on cancerous skin cells and mitochondria isolated from melanoma-induced animal model. Cutan Ocul Toxicol 2024:1-9. [PMID: 39392009 DOI: 10.1080/15569527.2024.2410355] [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: 06/24/2024] [Revised: 09/08/2024] [Accepted: 09/24/2024] [Indexed: 10/12/2024]
Abstract
INTRODUCTION Melanoma is still one of the deadliest cancers whose prevalence has increased in recent decades. Today, many polysaccharides and their bioactive compounds have been of special importance in modern biotechnology. They have various biological and therapeutic properties. they can regulate and strengthen the immune system, lower blood pressure and cholesterol, and reduce bacterial and viral infections. According to studies, these compounds also have antitumor properties. we investigated the cytotoxic effects of β-Glucan obtained from solid-state fermentation (SSF) of edible medicinal mushroom Lentinus edodes on cancerous skin cells. MATERIALS AND METHODS The mitochondria were isolated from melanoma cells via differential centrifugation and treated with various concentrations (30, 45, 60, 90, 120, and 240 µg/ml) of β-Glucan extract. Then, they were subjected to MTT, ROS, MMP decline, mitochondrial swelling, cytochrome c release, and flow cytometry assays. RESULTS The results of the MTT assay showed that IC50 of β-Glucan extract was 60 μg/ml, and it induced a selectively significant (P < 0.05) concentration-dependent decrease in the SDH activity in cancerous skin mitochondria. At higher concentrations, no such effect was observed. The ROS results also showed that 30, 45, and 60 µg/ml concentrations of β-Glucan extract significantly increased ROS. However, no such effect was observed at higher concentrations. MMP decline and the release of cytochrome c in cancer groups mitochondria and swelling were significantly increased at 30, 45, and 60 µg/ml compared to the control group. At higher concentrations, no such effect was observed. β-Glucan extract at 60 µg/ml concentration increased apoptosis on melanoma cells, while it had no effect on control non-tumour cells. DISCUSSION AND CONCLUSION Based on these results, β-Glucan extract at 30, 45, and 60 µg/ml showed a cytotoxic effect, while no such effect was observed at higher concentrations. Overall, it seems that β-Glucan has antioxidant and free radical scavenging effects on cancer cells at higher concentrations.
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Affiliation(s)
- Yalda Arast
- Research center of Environmental Pollutants, Qom University of Medical Sciences, Qom, Iran
| | - Hanife Esfandiari
- Department of Pharmacology and Toxicology, School of Pharmacy, Islamic Azad University of Medical Sciences, Tehran, Iran
| | - Farzane Kamranfar
- Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Mousavi
- Department of Pharmacology and Toxicology, School of Pharmacy, Islamic Azad University of Medical Sciences, Tehran, Iran
| | | | - Jalal Pourahmad
- Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Camilleri E, Blundell R, Baral B, Karpinski TM, Aruci E, Atrooz OM. A brief overview of the medicinal and nutraceutical importance of Inonotus obliquus (chaga) mushrooms. Heliyon 2024; 10:e35638. [PMID: 39170453 PMCID: PMC11336990 DOI: 10.1016/j.heliyon.2024.e35638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 07/31/2024] [Accepted: 08/01/2024] [Indexed: 08/23/2024] Open
Abstract
This literature review offers an extensive exploration of Chaga mushrooms (Inonotus obliquus), focusing on their phytochemical composition, health-promoting attributes, and mechanisms of action. The aim was to provide an up-to-date overview of Chaga's significance in the medicinal sector, emphasizing its potential role in diverse health benefits. The review highlights Chaga's remarkable anticancer, antioxidant, anti-diabetic, anti-inflammatory, antimicrobial, and immunomodulating properties. By synthesizing recent findings, this work underscores Chaga's importance in the medicinal industries and provides valuable insights into its pharmacological potential.
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Affiliation(s)
- Emma Camilleri
- Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Imsida, MSD2080, Malta
| | - Renald Blundell
- Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Imsida, MSD2080, Malta
- Centre for Molecular Medicine and Biobanking, University of Malta, MSD2080, Imsida, Malta
| | - Bikash Baral
- University of Helsinki, Helsinki, Finland
- Institute of Biological Resources (IBR), Kathmandu, Nepal
| | - Tomasz M. Karpinski
- Department of Medical Microbiology, Poznań University of Medical Sciences, Rokietnicka 10, 60-806, Poznań, Poland
| | - Edlira Aruci
- Western Balkans University, Autostrada Tirane-Durres km 7, Albania
| | - Omar M. Atrooz
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Al-Ahliyya Amman University, Amman, 19328, Jordan
- Department of Biological Sciences, Mutah University, P.O.Box(7), Mutah, Jordan
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Raal A, Kaldmäe H, Kütt K, Jürimaa K, Silm M, Bleive U, Aluvee A, Adamson K, Vester M, Erik M, Koshovyi O, Nguyen KV, Nguyen HT, Drenkhan R. Chemical Content and Cytotoxic Activity on Various Cancer Cell Lines of Chaga ( Inonotus obliquus) Growing on Betula pendula and Betula pubescens. Pharmaceuticals (Basel) 2024; 17:1013. [PMID: 39204121 PMCID: PMC11357148 DOI: 10.3390/ph17081013] [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: 07/02/2024] [Accepted: 07/23/2024] [Indexed: 09/03/2024] Open
Abstract
Chaga mushroom (Inonotus obliquus) is a pathogenic fungus that grows mostly on birch species (Betula pendula Roth and B. pubescens Ehrh.) and has traditionally been used as an anticancer medicine. This study aimed to compare the chemical composition and cytotoxic activity of chagas growing on both Betula spp. on various cancer cell lines. The freeze-dried extracts contained triterpenes inotodiol, lanosterol betulin, and betulinic acid typical to conks growing on Betula species. The cytotoxic activity of chaga growing on Betula pendula and B. pubescens 80% ethanolic extracts against 31 human cancer cell lines was evaluated by a sulforhodamine B assay. Chaga extract showed moderate activity against all cancer cell lines examined; it did not result in high cytotoxicity (IC50 ≤ 20 µg/mL). The strongest inhibitions were observed with chaga (growing on B. pendula) extract on the HepG2 and CAL-62 cell line and with chaga (from B. pubescens) extract on the HepG2 cell line, with IC50 values of 37.71, 43.30, and 49.99 μg/mL, respectively. The chaga extracts from B. pendula exert somewhat stronger effects on most cancer cell lines studied than B. pubescens extracts, which can be attributed to a higher content of inotodiol in B. pendula extracts. This study highlights the potential of chaga as a source of bioactive compounds with selective anticancer properties. To the best of our knowledge, this study is the first investigation of the chemical composition of I. obliquus parasitizing on B. pubescens.
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Affiliation(s)
- Ain Raal
- Institute of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia;
| | - Hedi Kaldmäe
- Polli Horticultural Research Centre, Chair of Horticulture, Institute of Agricultural and Environmental Sciences, Estonian University of Life Sciences, Uus 2, Polli, 69108 Mulgi Parish, Estonia; (H.K.); (U.B.); (A.A.)
| | - Karin Kütt
- Institute of Forestry and Engineering, Chair of Silviculture and Forest Ecology, Estonian University of Life Sciences, Kreutzwaldi 5, 51006 Tartu, Estonia; (K.K.); (K.J.); (K.A.); (M.V.); (R.D.)
| | - Katrin Jürimaa
- Institute of Forestry and Engineering, Chair of Silviculture and Forest Ecology, Estonian University of Life Sciences, Kreutzwaldi 5, 51006 Tartu, Estonia; (K.K.); (K.J.); (K.A.); (M.V.); (R.D.)
| | - Maidu Silm
- Institute of Agricultural and Environmental Sciences, Estonian University of Life Sciences, Kreutzwaldi 5, 51006 Tartu, Estonia;
| | - Uko Bleive
- Polli Horticultural Research Centre, Chair of Horticulture, Institute of Agricultural and Environmental Sciences, Estonian University of Life Sciences, Uus 2, Polli, 69108 Mulgi Parish, Estonia; (H.K.); (U.B.); (A.A.)
| | - Alar Aluvee
- Polli Horticultural Research Centre, Chair of Horticulture, Institute of Agricultural and Environmental Sciences, Estonian University of Life Sciences, Uus 2, Polli, 69108 Mulgi Parish, Estonia; (H.K.); (U.B.); (A.A.)
| | - Kalev Adamson
- Institute of Forestry and Engineering, Chair of Silviculture and Forest Ecology, Estonian University of Life Sciences, Kreutzwaldi 5, 51006 Tartu, Estonia; (K.K.); (K.J.); (K.A.); (M.V.); (R.D.)
| | - Marili Vester
- Institute of Forestry and Engineering, Chair of Silviculture and Forest Ecology, Estonian University of Life Sciences, Kreutzwaldi 5, 51006 Tartu, Estonia; (K.K.); (K.J.); (K.A.); (M.V.); (R.D.)
| | | | - Oleh Koshovyi
- Institute of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia;
| | - Khan Viet Nguyen
- Faculty of Pharmacy, Hue University of Medicine and Pharmacy, Hue University, 06 Ngo Quyen, Hue City 530000, Vietnam; (K.V.N.); (H.T.N.)
| | - Hoai Thi Nguyen
- Faculty of Pharmacy, Hue University of Medicine and Pharmacy, Hue University, 06 Ngo Quyen, Hue City 530000, Vietnam; (K.V.N.); (H.T.N.)
| | - Rein Drenkhan
- Institute of Forestry and Engineering, Chair of Silviculture and Forest Ecology, Estonian University of Life Sciences, Kreutzwaldi 5, 51006 Tartu, Estonia; (K.K.); (K.J.); (K.A.); (M.V.); (R.D.)
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Yeo D, Yun YG, Shin SJ, Dashnyam K, Khurelbaatar A, Lee JH, Kim HW. Chaga mushroom extract suppresses oral cancer cell growth via inhibition of energy metabolism. Sci Rep 2024; 14:10616. [PMID: 38720012 PMCID: PMC11078932 DOI: 10.1038/s41598-024-61125-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 05/02/2024] [Indexed: 05/12/2024] Open
Abstract
Oral cancer stands as a prevalent maligancy worldwide; however, its therapeutic potential is limited by undesired effects and complications. As a medicinal edible fungus, Chaga mushroom (Inonotus obliquus) exhibits anticancer effects across diverse cancers. Yet, the precise mechanisms underlying its efficacy remain unclear. We explored the detailed mechanisms underlying the anticancer action of Chaga mushroom extract in oral cancer cells (HSC-4). Following treatment with Chaga mushroom extracts, we analyzed cell viability, proliferation capacity, glycolysis, mitochondrial respiration, and apoptosis. Our findings revealed that the extract reduced cell viability and proliferation of HSC-4 cells while arresting their cell cycle via suppression of STAT3 activity. Regarding energy metabolism, Chaga mushroom extract inhibited glycolysis and mitochondrial membrane potential in HSC-4 cells, thereby triggering autophagy-mediated apoptotic cell death through activation of the p38 MAPK and NF-κB signaling pathways. Our results indicate that Chaga mushroom extract impedes oral cancer cell progression, by inhibiting cell cycle and proliferation, suppressing cancer cell energy metabolism, and promoting autophagy-mediated apoptotic cell death. These findings suggest that this extract is a promising supplementary medicine for the treatment of patients with oral cancer.
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Affiliation(s)
- Donghyeon Yeo
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119, Dandae-ro, Cheonan, 31116, Republic of Korea
- Department of Nanobiomedical Science and BK21 Four NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea
| | - Yeo Gyun Yun
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119, Dandae-ro, Cheonan, 31116, Republic of Korea
- Department of Nanobiomedical Science and BK21 Four NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea
| | - Seong-Jin Shin
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119, Dandae-ro, Cheonan, 31116, Republic of Korea
- Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea
| | - Khandmaa Dashnyam
- Drug Research Institute, Mongolian University of Pharmaceutical Science, Ulaanbaatar, 18130, Mongolia
| | - Anand Khurelbaatar
- Drug Research Institute, Mongolian University of Pharmaceutical Science, Ulaanbaatar, 18130, Mongolia
| | - Jun Hee Lee
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119, Dandae-ro, Cheonan, 31116, Republic of Korea.
- Department of Nanobiomedical Science and BK21 Four NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea.
- Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea.
- Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea.
| | - Hae-Won Kim
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119, Dandae-ro, Cheonan, 31116, Republic of Korea.
- Department of Nanobiomedical Science and BK21 Four NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea.
- Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea.
- Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea.
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea.
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Amin FG, Elfiky AA, Nassar AM. In silico targeting of SARS-CoV-2 spike receptor-binding domain from different variants with chaga mushroom terpenoids. J Biomol Struct Dyn 2024; 42:1079-1087. [PMID: 37042960 DOI: 10.1080/07391102.2023.2199084] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 03/30/2023] [Indexed: 04/13/2023]
Abstract
Terpenoids from the chaga mushroom have been identified as potential antiviral agents against SARS-CoV-2. This is because it can firmly bind to the viral spike receptor binding domain (RBD) and the auxiliary host cell receptor glucose-regulated protein 78 (GRP78). The current work examines the association of the chaga mushroom terpenoids with the RBD of various SARS-CoV-2 variants, including alpha, beta, gamma, delta, and omicron. This association was compared to the SARS-CoV-2 wild-type (WT) RBD using molecular docking analysis and molecular dynamics modeling. The outcomes demonstrated that the mutant RBDs, which had marginally greater average binding affinities (better binding) than the WT, were successfully inhibited by the chaga mushroom terpenoids. The results suggest that the chaga mushroom can be effective against various SARS-CoV-2 variants by targeting both the host-cell surface receptor GRP78 and the viral spike RBD.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Fatma G Amin
- Physics Department, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Abdo A Elfiky
- Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Aaya M Nassar
- Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt
- Department of Clinical Research and Leadership, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA
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Fordjour E, Manful CF, Javed R, Galagedara LW, Cuss CW, Cheema M, Thomas R. Chaga mushroom: a super-fungus with countless facets and untapped potential. Front Pharmacol 2023; 14:1273786. [PMID: 38116085 PMCID: PMC10728660 DOI: 10.3389/fphar.2023.1273786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 10/16/2023] [Indexed: 12/21/2023] Open
Abstract
Inonotus obliquus (Chaga mushroom) is an inexpensive fungus with a broad range of traditional and medicinal applications. These applications include therapy for breast, cervix, and skin cancers, as well as treating diabetes. However, its benefits are virtually untapped due to a limited understanding of its mycochemical composition and bioactivities. In this article, we explore the ethnobotany, mycochemistry, pharmacology, traditional therapeutic, cosmetic, and prospective agricultural uses. The review establishes that several secondary metabolites, such as steroids, terpenoids, and other compounds exist in chaga. Findings on its bioactivity have demonstrated its ability as an antioxidant, anti-inflammatory, antiviral, and antitumor agent. The study also demonstrates that Chaga powder has a long history of traditional use for medicinal purposes, pipe smoking rituals, and mystical future forecasts. The study further reveals that the applications of Chaga powder can be extended to industries such as pharmaceuticals, food, cosmetics, and agriculture. However numerous publications focused on the pharmaceutical benefits of Chaga with few publications on other applications. Overall, chaga is a promising natural resource with a wide range of potential applications and therefore the diverse array of therapeutic compounds makes it an attractive candidate for various applications such as plant biofertilizers and active ingredients in cosmetics and pharmaceutical products. Thus, further exploration of Chaga's potential benefits in agriculture and other industries could lead to exciting new developments and innovations.
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Affiliation(s)
- Eric Fordjour
- Biotron Experimental Climate Change Research Centre, Department of Biology, University of Western Ontario, London, ON, Canada
| | - Charles F. Manful
- School of Science and the Environment, Grenfell Campus, Memorial University of Newfoundland, Corner Brook, NL, Canada
| | - Rabia Javed
- School of Science and the Environment, Grenfell Campus, Memorial University of Newfoundland, Corner Brook, NL, Canada
| | - Lakshman W. Galagedara
- School of Science and the Environment, Grenfell Campus, Memorial University of Newfoundland, Corner Brook, NL, Canada
| | - Chad W. Cuss
- School of Science and the Environment, Grenfell Campus, Memorial University of Newfoundland, Corner Brook, NL, Canada
| | - Mumtaz Cheema
- Biotron Experimental Climate Change Research Centre, Department of Biology, University of Western Ontario, London, ON, Canada
| | - Raymond Thomas
- Biotron Experimental Climate Change Research Centre, Department of Biology, University of Western Ontario, London, ON, Canada
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Won GW, Lee SH, Bhatta MP, Choi SH, Oh CH, Park JT, Park JI. Preventive effects of inotodiol on polyinosinic-polycytidylic acid-induced inflammation in human dermal fibroblasts. Heliyon 2023; 9:e20556. [PMID: 37886743 PMCID: PMC10597809 DOI: 10.1016/j.heliyon.2023.e20556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 08/21/2023] [Accepted: 09/28/2023] [Indexed: 10/28/2023] Open
Abstract
Double-strand RNA(dsRNA), which can induce inflammation, can be generated by necrotic keratinocytes in the skin environment. As an analog of dsRNA, polyinosinic-polycytidylic acid (poly(I:C)) is used to induce inflammation via the Toll-like Receptor 3 (TLR3) signaling pathway. Inotodiol, isolated from Inonotus obliquus, known as Chaga mushroom, is a natural lanostane-type triterpenoid with significant pharmacological activity and notable anti-inflammatory effects. However, the functions of inotodiol on dsRNA-induced inflammation in human dermal fibroblast (HDFs) remains unclear. In this study, we evaluated the anti-inflammatory effects of inotodiol inflammation induced on by poly(I:C) in HDFs. After pre-treatment with inotodiol, poly (I:C) was used to induce inflammation. Subsequently, mRNA expression and protein secretion of inflammatory cytokines, as well as TLR3 signaling protein levels were assessed. Inflammatory cytokines IL-1β, IL-6, and TNF-α's increased mRNA expression by poly(I:C) in HDFs was significantly suppressed in the inotodiol pre-treatment group in a dose-dependent manner. A similar pattern was evaluated in the protein levels of these three cytokines. The inflammatory signals of TLR3 via p-IKK, p-p38, and NF-κB was reduced by inotodiol pre-treatment. Taken together, inotodiol possesses strong anti-inflammatory activity against poly(I:C)-induced inflammation in HDFs. Therefore, our findings support potential application of inotodiol as an effective anti-inflammatory agent in cosmetics.
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Affiliation(s)
- Gun-Woo Won
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea
- BK 21 FOUR, Chungnam National University Department of Medical Science, Daejeon, Republic of Korea
| | - Seung Hoon Lee
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea
- Translational Immunology Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Mahesh Prakash Bhatta
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea
| | - Seung-Hyeon Choi
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea
- Translational Immunology Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Cheong-Hae Oh
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea
| | - Jong-Tae Park
- Department of Food Science and Technology, Chungnam National University, Daejeon, 34134, Republic of Korea
- CARBOEXPERT Inc., Daejeon, 34134, Republic of Korea
| | - Jong-Il Park
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea
- Translational Immunology Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea
- BK 21 FOUR, Chungnam National University Department of Medical Science, Daejeon, Republic of Korea
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10
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Sułkowska-Ziaja K, Robak J, Szczepkowski A, Gunia-Krzyżak A, Popiół J, Piotrowska J, Rospond B, Szewczyk A, Kała K, Muszyńska B. Comparison of Bioactive Secondary Metabolites and Cytotoxicity of Extracts from Inonotus obliquus Isolates from Different Host Species. Molecules 2023; 28:4907. [PMID: 37446570 DOI: 10.3390/molecules28134907] [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: 05/03/2023] [Revised: 06/10/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Inonotus obliquus, a wood-decaying mushroom, has been used as a health-promoting supplement and nutraceutical for centuries. It is a source of bioactive compounds accumulated in both the conks (pseudosclerotia/sclerotia) and the biomass obtained in vitro. This study aimed to qualitatively and quantitatively analyze the bioelements and selected metabolites produced in mycelial cultures obtained from different host species. The mycochemical potential of mycelial cultures isolated from pseudosclerotia grown in Betula pendula, Alnus glutinosa, and Carpinus betulus was compared. Parent cultures were obtained in two types of medium (malt extract agar substrates without and with birch wood). Experimental cultures were developed in 2 L bioreactors for 10 days. The content of bioelements was determined using FAAS and FAES methods. Organic compounds were estimated using the RP-HPLC-DAD method. The cytotoxicity of the extracts was evaluated in human keratinocytes HaCaT, human skin fibroblasts BJ, human liver cancer HepG2, human melanoma A375, and mouse melanoma B16-F10. The extracts showed the presence of bioelements: sodium, potassium, magnesium, calcium, zinc, manganese, iron, and copper; phenolic acids: p-hydroxybenzoic, caffeic, p-coumaric, and protocatechuic; sterols: lanosterol, ergosterol, ergosterol peroxide; triterpene compounds: betulin, betulinic acid, inotodiol; indole compounds: L-tryptophan, tryptamine, 5-methyltryptamine, melatonin. The content of bioactive substances in the biomass was dependent on both the origin of the host species of the fungus isolate and the type of culture medium. Based on the results of this study, mycelial cultures can be proposed as a potential source of bioactive compounds and are promising naturally derived cytotoxic agents.
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Affiliation(s)
- Katarzyna Sułkowska-Ziaja
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
| | - Justyna Robak
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
| | - Andrzej Szczepkowski
- Institute of Forest Sciences, Department of Forest Protection, Warsaw University of Life Sciences-SGGW, Nowoursynowska 159, 02-776 Warszawa, Poland
| | - Agnieszka Gunia-Krzyżak
- Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
| | - Justyna Popiół
- Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
| | - Joanna Piotrowska
- Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
| | - Bartłomiej Rospond
- Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
| | - Agnieszka Szewczyk
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
| | - Katarzyna Kała
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
| | - Bożena Muszyńska
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
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Abugomaa A, Elbadawy M, Ishihara Y, Yamamoto H, Kaneda M, Yamawaki H, Shinohara Y, Usui T, Sasaki K. Anti-cancer activity of Chaga mushroom ( Inonotus obliquus) against dog bladder cancer organoids. Front Pharmacol 2023; 14:1159516. [PMID: 37153767 PMCID: PMC10154587 DOI: 10.3389/fphar.2023.1159516] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 04/10/2023] [Indexed: 05/10/2023] Open
Abstract
Despite its disadvantages, chemotherapy is still commonly used for the treatment of bladder cancer (BC). Developing natural supplements that can target cancer stem cells (CSCs) which cause drug resistance and distant metastasis is necessary. Chaga mushrooms are popular to have several health-promoting and anti-cancer potentials. Organoid culture can recapitulate tumor heterogeneity, epithelial environment, and genetic and molecular imprints of the original tissues. In the previous study, we generated dog bladder cancer organoids (DBCO) as a novel experimental model of muscle-invasive BCO. Therefore, the present study aimed to examine the anti-tumor potentials of Chaga mushroom extract (Chaga) against DBCO. Four strains of DBCO were used in the present study. Treatment with Chaga inhibited the cell viability of DBCO in a concentration-dependent way. Treatment of DBCO with Chaga has significantly arrested its cell cycle and induced apoptosis. Expression of bladder CSC markers, CD44, C-MYC, SOX2, and YAP1, declined in the Chaga-treated DBCO. Also, Chaga inhibited the phosphorylation of ERK in DBCO. Expression of downstream signals of ERK, C-MYC, and Cyclins (Cyclin-A2, Cyclin-D1, Cyclin-E1, and CDK4) was also inhibited by Chaga in DBCO. Interestingly, the combinational treatment of DBCO with Chaga and anti-cancer drugs, vinblastine, mitoxantrone, or carboplatin, showed a potentiating activity. In vivo, Chaga administration decreased tumor growth and weight of DBCO-derived xenograft in mice with the induction of necrotic lesions. In conclusion, Chaga diminished the cell viability of DBCO by inhibiting proliferation-related signals and stemness conditions as well as by arresting the cell cycle. Collectively, these data suggest the value of Chaga as a promising natural supplement that could potentiate the effect of adjuvant chemotherapy, lower its adverse effects, and thus, limit the recurrence and metastasis of BC.
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Affiliation(s)
- Amira Abugomaa
- Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan
- Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Mohamed Elbadawy
- Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan
- Department of Pharmacology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Egypt
| | - Yusuke Ishihara
- Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Haru Yamamoto
- Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Masahiro Kaneda
- Laboratory of Veterinary Anatomy, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Hideyuki Yamawaki
- Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori, Japan
| | - Yuta Shinohara
- Pet Health & Food Division, Iskara Industry Co., Ltd., Tokyo, Japan
| | - Tatsuya Usui
- Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Kazuaki Sasaki
- Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan
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STIL Promotes Tumorigenesis of Bladder Cancer by Activating PI3K/AKT/mTOR Signaling Pathway and Targeting C-Myc. Cancers (Basel) 2022; 14:cancers14235777. [PMID: 36497260 PMCID: PMC9739707 DOI: 10.3390/cancers14235777] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 11/19/2022] [Accepted: 11/20/2022] [Indexed: 11/25/2022] Open
Abstract
SCL/TAL1 interrupting locus (STIL) regulates centriole replication and causes chromosome instability, which is closely related to malignant tumors. The purpose of our study was to investigate the role of STIL in bladder cancer (BC) tumorigenesis for the first time. The public database indicated that STIL is highly expressed and correlated with the cell cycle in BC. Immunohistochemistry staining showed that STIL expression is significantly elevated in BC tissues compared with paracancer tissues. CRISPR-Cas9 gene editing technology was used to induce BC cells to express STIL-specific sgRNA, revealing a significantly delayed growth rate in STIL knockout BC cells. Moreover, cell cycle arrest in the G0/G1 phase was triggered by decreasing STIL, which led to delayed BC cell growth in vitro and in vivo. Mechanically, STIL knockout inhibited the PI3K/AKT/mTOR pathway and down-regulated the expression of c-myc. Furthermore, SC79 (AKT activating agent) partially reversed the inhibitory effects of STIL knockout on the proliferation and migration of BC cells. In conclusion, STIL enhanced the PI3K/AKT/mTOR pathway, resulting in increased expression of c-myc, ultimately promoting BC occurrence and progression. These results indicate that STIL might be a potential target for BC patients.
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Jin J, Yang H, Hu L, Wang Y, Wu W, Hu C, Wu K, Wu Z, Cheng W, Huang Y. Inonotsuoxide B suppresses hepatic stellate cell activation and proliferation via the PI3K/AKT and ERK1/2 pathway. Exp Ther Med 2022; 23:417. [PMID: 35601068 DOI: 10.3892/etm.2022.11344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 08/04/2020] [Indexed: 11/05/2022] Open
Affiliation(s)
- Juan Jin
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230032, P.R. China
| | - Hui Yang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230032, P.R. China
| | - Lili Hu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230032, P.R. China
| | - Yinghong Wang
- Department of Pharmacy, Division of Life Sciences and Medicine, Anhui Provincial Cancer Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230001, P.R. China
| | - Wenyong Wu
- Department of General Surgery, Anhui No. 2 Provincial People's Hospital, Hefei, Anhui 230041, P.R. China
| | - Chengmu Hu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230032, P.R. China
| | - Kun Wu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230032, P.R. China
| | - Zehua Wu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230032, P.R. China
| | - Wenming Cheng
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230032, P.R. China
| | - Yan Huang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230032, P.R. China
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Azfaralariff A, Farahfaiqah F, Shahid M, Sanusi SA, Law D, Mohd Isa AR, Muhamad M, Tsui TT, Fazry S. Marantodes pumilum: Systematic computational approach to identify their therapeutic potential and effectiveness. JOURNAL OF ETHNOPHARMACOLOGY 2022; 283:114751. [PMID: 34662662 DOI: 10.1016/j.jep.2021.114751] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 09/30/2021] [Accepted: 10/13/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Marantodes pumilum (MP) herbs, locally known as Kacip Fatimah, are widely used traditionally to improve women's health. The herb is frequently used for gynecological issues such as menstrual problems, facilitating and quickening delivery, post-partum medication, treats flatulence and dysentery, and. MP extracts are thought to aid in the firming and toning of abdominal muscles, tighten breasts and vaginal muscles, and anti-dysmenorrhea. It also was used for the treatment of gonorrhea and hemorrhoids. As MP product has been produced commercially recently, more in-depth studies should be conducted. The presence of numerous active compounds in MP might provide a synergistic effect and potentially offer other health benefits than those already identified and known. AIM OF THE STUDY This study aimed to use a computational target fishing approach to predict the possible therapeutic effect of Marantodes pumilum and evaluated their effectivity. MATERIALS AND METHODS This study involves a computational approach to identify the potential targets by using target fishing. Several databases were used: PubChem database to obtain the chemical structure of interested compounds; Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) server and the SWISSADME web tool to identify and select the compounds having drug-likeness properties; PharmMapper was used to identify top ten target protein of the selected compounds and Online Mendelian Inheritance in Man (OMIM) was used to predict human genetic problems; the gene id of top-10 proteins was obtained from UniProtKB to be analyzed by using GeneMANIA server to check the genes' function and their co-expression; Gene Pathway established by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) of the selected targets were analyzed by using EnrichR server and confirmed by using DAVID (The Database for Annotation, Visualization and Integrated Discovery) version 6.8 and STRING database. All the interaction data was analyzed by Cytoscape version 3.7.2 software. The protein structure of most putative proteins was obtained from the RCSB protein data bank. Thedocking analysis was conducted using PyRx biological software v0.8 and illustrated by BIOVIA Discovery Studio Visualizer version 20.1.0. As a preliminary evaluation, a cell viability assay using Sulforhodamine B was conducted to evaluate the potential of the predicted therapeutic effect. RESULTS It was found that four studied compounds are highly correlated with three proteins: EFGR, CDK2, and ESR1. These proteins are highly associated with cancer pathways, especially breast cancer and prostate cancer. Qualitatively, cell proliferation assay conducted shown that the extract has IC50 of 88.69 μg/ml against MCF-7 and 66.51 μg/ml against MDA-MB-231. CONCLUSIONS Natural herbs are one of the most common forms of complementary and alternative medicine, and they play an important role in disease treatment. The results of this study show that in addition to being used traditionally to maintain women's health, the use of Marantodes pumilum indirectly has the potential to protect against the development of cancer cells, especially breast cancer. Therefore, further research is necessary to confirm the potential of this plant to be used in the development of anti-cancer drugs, especially for breast cancer.
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Affiliation(s)
- Ahmad Azfaralariff
- Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor, Malaysia
| | - Fazial Farahfaiqah
- Faculty of Chemical Engineering Technology, Universiti Malaysia Perlis (UNIMAP), Perlis, Malaysia
| | - Muhamad Shahid
- Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor, Malaysia
| | - Siti Aisyah Sanusi
- Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor, Malaysia
| | - Douglas Law
- Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor, Malaysia; Faculty of Health and Life Sciences, Inti International University, Persiaran Perdana BBN Putra Nilai, 71800, Nilai, Negeri Sembilan, Malaysia
| | - Abdul Razak Mohd Isa
- Medika Natura Sdn. Bhd., No 44B, Jalan Bola Tampar, 13/14, Seksyen 13, Shah Alam, Selangor, Malaysia
| | - Mustadza Muhamad
- Medika Natura Sdn. Bhd., No 44B, Jalan Bola Tampar, 13/14, Seksyen 13, Shah Alam, Selangor, Malaysia
| | - Tee Thiam Tsui
- ZACH Biotech Depot Sdn. Bhd., No. 19-2, Jalan SC 5/A, Kawasan Perindustrian Sg. Chua, 43000, Kajang, Selangor, Malaysia
| | - Shazrul Fazry
- Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor, Malaysia; Tasik Chini Research Centre, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor, Malaysia.
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15
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NHI NTN, KHANG DT, DUNG TN. Termitomyces mushroom extracts and its biological activities. FOOD SCIENCE AND TECHNOLOGY 2022. [DOI: 10.1590/fst.125921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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16
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Nowakowski P, Markiewicz-Żukowska R, Bielecka J, Mielcarek K, Grabia M, Socha K. Treasures from the forest: Evaluation of mushroom extracts as anti-cancer agents. Biomed Pharmacother 2021; 143:112106. [PMID: 34482165 DOI: 10.1016/j.biopha.2021.112106] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/09/2021] [Accepted: 08/23/2021] [Indexed: 12/16/2022] Open
Abstract
Mushrooms provide a reliable source of bioactive compounds and have numerous nutritional values, which is one of the reasons why they are widely used for culinary purposes. They may also be a remedy for several medical conditions, including cancer diseases. Given the constantly increasing number of cancer incidents, the great anticancer potential of mushrooms has unsurprisingly become an object of interest to researchers. Therefore, this review aimed to collect and summarize all the available scientific data on the anti-cancer activity of mushroom extracts. Our research showed that mushroom extracts from 92 species, prepared using 12 different solvents, could reduce the viability of 38 various cancers. Additionally, we evaluated different experimental models: in vitro (cell model), in vivo (mice and rat model, case studies and randomized controlled trials), and in silico. Breast cancer proved to be sensitive to the highest number of mushroom extracts. The curative mechanisms of the studied mushrooms consisted in: inhibition of cancer cell proliferation, unregulated proportion of cells in cell cycle phases, induction of autophagy and phagocytosis, improved response of the immune system, and induction of apoptotic death of cells via upregulation of pro-apoptotic factors and downregulation of anti-apoptotic genes. The processes mainly involved the expression of caspases -3, -8, -9, AKT, p27, p53, BAX, and BCL2. The quoted results could lead to the classification of mushrooms as nutraceuticals used to prevent a variety of disorders or to support treatment of cancer diseases.
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Affiliation(s)
- Patryk Nowakowski
- Department of Bromatology, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, Mickiewicza 2D, 15-222 Białystok, Poland.
| | - Renata Markiewicz-Żukowska
- Department of Bromatology, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, Mickiewicza 2D, 15-222 Białystok, Poland
| | - Joanna Bielecka
- Department of Bromatology, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, Mickiewicza 2D, 15-222 Białystok, Poland
| | - Konrad Mielcarek
- Department of Bromatology, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, Mickiewicza 2D, 15-222 Białystok, Poland
| | - Monika Grabia
- Department of Bromatology, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, Mickiewicza 2D, 15-222 Białystok, Poland
| | - Katarzyna Socha
- Department of Bromatology, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, Mickiewicza 2D, 15-222 Białystok, Poland
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17
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Lee MG, Kwon YS, Nam KS, Kim SY, Hwang IH, Kim S, Jang H. Chaga mushroom extract induces autophagy via the AMPK-mTOR signaling pathway in breast cancer cells. JOURNAL OF ETHNOPHARMACOLOGY 2021; 274:114081. [PMID: 33798660 DOI: 10.1016/j.jep.2021.114081] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 03/04/2021] [Accepted: 03/25/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Chaga mushrooms (Inonotus obliquus) are commonly used in traditional treatments in Eastern Europe and Asia due to their diverse pharmacological effects, including anti-tumor and immunologic effects. Thus, many cancer patients take Chaga mushrooms as a complementary medicine, even during chemotherapy or radiotherapy. However, few studies have investigated the effects or molecular targets of Chaga mushrooms in breast cancer. AIM OF THE STUDY Herein, we examined the anticancer effects of Chaga mushrooms in different types of breast cancer cell lines, and explored the underlying molecular mechanism to better understand their effects and benefits. MATERIALS AND METHODS Chaga mushroom extract (CME) was prepared by extracting Chaga mushrooms with 70% ethanol. The cytotoxic effects of CME were assessed by MTT assay and protein expressions were evaluated by western blotting. To evaluate in vivo anti-tumor effects of CME, CME (2 g/kg) was orally administered to 4T1 tumor-bearing BALB/c mice every other day over 30 days (15 administrations), and tumor sizes were measured. Silica gel column chromatography was used to fractionate CME, and major constituents responsible for cytotoxic effects of CME were identified by 1H/13C-NMR and LC-MS. RESULTS CME inhibited the proliferation of 4T1 mouse breast cancer cells in a dose and time-dependent manner. The expression of LC3 and phosphorylation of AMPK were increased by CME, while the phosphorylation of mTOR, S6, and S6K1 were suppressed, suggesting that CME induced autophagy by activating AMPK and inhibiting mTOR signaling pathways. Consistent with its observed cytotoxic effect in vitro, CME effectively suppressed tumor growth in 4T1 tumor-bearing BALB/c mice. In addition, inotodiol and trametenolic acid were identified as the major constituents responsible for the cytotoxic effects of CME on breast cancer cells. Moreover, inotodiol and trametenolic acid-enriched fractions both exhibited cytotoxic effects regardless of breast cancer cell subtypes and did not interfere with the cytotoxic effects of conventional drugs. CONCLUSIONS Taken together, Chaga mushroom extract induced autophagy by activating AMPK and inhibiting the mTOR signaling pathway. Our data suggest Chaga mushrooms may be a beneficial complementary medicine for breast cancer patients.
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Affiliation(s)
- Min-Gu Lee
- Department of Pharmacology, College of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju, Gyeongsangbuk-do, 38066, Republic of Korea
| | - Yun-Suk Kwon
- Department of Pharmacology, College of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju, Gyeongsangbuk-do, 38066, Republic of Korea
| | - Kyung-Soo Nam
- Department of Pharmacology, College of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju, Gyeongsangbuk-do, 38066, Republic of Korea
| | - Seo Yeon Kim
- Department of Pharmacy, Woosuk University, 443 Samnye-ro, Wanju, Jeollabuk-do, 55338, Republic of Korea
| | - In Hyun Hwang
- Department of Pharmacy, Woosuk University, 443 Samnye-ro, Wanju, Jeollabuk-do, 55338, Republic of Korea
| | - Soyoung Kim
- Department of Pharmacology, College of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju, Gyeongsangbuk-do, 38066, Republic of Korea.
| | - Hyunsoo Jang
- Department of Radiation Oncology, College of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju, Gyeongsangbuk-do, 38066, Republic of Korea.
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β-Glucan: A dual regulator of apoptosis and cell proliferation. Int J Biol Macromol 2021; 182:1229-1237. [PMID: 33991557 DOI: 10.1016/j.ijbiomac.2021.05.065] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/26/2021] [Accepted: 05/10/2021] [Indexed: 01/09/2023]
Abstract
β-Glucans are polysaccharides generally obtained from the cell wall of bacteria, fungi, yeasts, and aleurone layer of cereals. β-Glucans are polymers, with β-1,3 glucose as core linear structure, but they differ in their main branch length, linkages and branching patterns, giving rise to high and low-molecular-weight β-glucans. They are well-known cell response modifiers with immune-modulating, nutraceutical and health beneficial effects, including anticancer and pro-apoptotic properties. β-Glucan extracts have shown positive responses in controlling tumor cell proliferation and activation of the immune system. The immunomodulatory action of β-glucans enhances the host's antitumor defense against cancer. In consonance with the above, many studies have shown that β-glucan treatment leads to the induction of apoptotic death of cancer cells. The ability of β-glucans to stimulate apoptotic pathways or the proteins involved in apoptosis prompting a new domain in cancer therapy. β-glucan can be a potential therapeutic agent for the treatment of cancer. However, there is a need to legitimize the β-glucan type, as most of the studies include β-glucan from different sources having different physicochemical properties. The body of literature presented here focuses on the effects of β-glucan on immunomodulation, proliferation, cell death and the possible mechanisms and pathways involved in these processes.
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Victor D, Peter S. Accumulation and distribution of 40K in the chaga mushroom. MYCOSCIENCE 2021; 62:81-86. [PMID: 37089251 PMCID: PMC9157780 DOI: 10.47371/mycosci.2020.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 11/04/2020] [Accepted: 11/08/2020] [Indexed: 11/16/2022]
Abstract
This work is the first report on activity concentrations of 40K in Inonotus obliquus sampled in a virgin forest of Siberia. The results have shown that the chaga conk is characterized by high activity concentrations of 40K, averaging 1,641 Bq/kg dry weight (DW) and peaking at 3,502 Bq/kg DW. Activity concentrations of 40K in chaga conks have been defined to increase from the near-trunk stratum to the crust of the conk with increased exposure to the solar radiation. Our measurements have revealed the samples to be mildly contaminated with 137Cs. Intensive assimilation of 40K by chaga conks has been shown as a normal and innate feature of the wild chaga mushroom.
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Affiliation(s)
| | - Sobakin Peter
- Institute for Biological Problems of Cryolithozone, SB, RAS
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20
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Lin L, Xu J. Fungal Pigments and Their Roles Associated with Human Health. J Fungi (Basel) 2020; 6:E280. [PMID: 33198121 PMCID: PMC7711509 DOI: 10.3390/jof6040280] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 11/08/2020] [Accepted: 11/09/2020] [Indexed: 12/19/2022] Open
Abstract
Fungi can produce myriad secondary metabolites, including pigments. Some of these pigments play a positive role in human welfare while others are detrimental. This paper reviews the types and biosynthesis of fungal pigments, their relevance to human health, including their interactions with host immunity, and recent progresses in their structure-activity relationships. Fungal pigments are grouped into carotenoids, melanin, polyketides, and azaphilones, etc. These pigments are phylogenetically broadly distributed. While the biosynthetic pathways for some fungal pigments are known, the majority remain to be elucidated. Understanding the genes and metabolic pathways involved in fungal pigment synthesis is essential to genetically manipulate the production of both the types and quantities of specific pigments. A variety of fungal pigments have shown wide-spectrum biological activities, including promising pharmacophores/lead molecules to be developed into health-promoting drugs to treat cancers, cardiovascular disorders, infectious diseases, Alzheimer's diseases, and so on. In addition, the mechanistic elucidation of the interaction of fungal pigments with the host immune system provides valuable clues for fighting fungal infections. The great potential of fungal pigments have opened the avenues for academia and industries ranging from fundamental biology to pharmaceutical development, shedding light on our endeavors for disease prevention and treatment.
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Affiliation(s)
- Lan Lin
- School of Life Science and Technology, Department of Bioengineering, Key Laboratory of Developmental Genes and Human Diseases (MOE), Southeast University, Nanjing 210096, Jiangsu, China;
- Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada
| | - Jianping Xu
- Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada
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21
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Szychowski KA, Skóra B, Pomianek T, Gmiński J. Inonotus obliquus - from folk medicine to clinical use. J Tradit Complement Med 2020; 11:293-302. [PMID: 34195023 PMCID: PMC8240111 DOI: 10.1016/j.jtcme.2020.08.003] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 08/18/2020] [Accepted: 08/19/2020] [Indexed: 12/19/2022] Open
Abstract
The Inonotus obliquus (I. obliquus) mushroom was traditionally used to treat various gastrointestinal diseases. For many years, mounting evidence has indicated the potential of I. obliquus extracts for treatment of viral and parasitic infections. Furthermore, substances from I. obiquus have been shown to stimulate the immune system. The most promising finding was the demonstration that I. obliquus has hypoglycemic and insulin sensitivity potential. This review summarizes the therapeutic potential of I. obliquus extracts in counteracting the progression of cancers and diabetes mellitus as well as their antiviral and antiparasitic activities and antioxidant role. As shown by literature data, various authors have tried to determine the molecular mechanism of action of I. obliquus extracts. Two mechanisms of action of I. obliquus extracts are currently emerging. The first is associated with the broad-sense impact on antioxidant enzymes and the level of reactive oxygen species (ROS). The other is related to peroxisome proliferator-activated receptor gamma (PPARγ) effects. This receptor may be a key factor in the anti-inflammatory, antioxidant, and anti-cancer activity of I. obliquus extracts. It can be concluded that I. obliquus fits the definition of functional food and has a potentially positive effect on health beyond basic nutrition; however, studies that meet the evidence-based medicine (EBM) criteria are needed.
Extracts or polysaccharides from I. obliquus exhibit an anti-cancer potential in vitro. Extracts or polysaccharides from I. obliquus exhibit anti-inflammation potential. Extracts or polysaccharides from I. obliquus exhibit hypoglycemic and insulin sensitivity potential.
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Affiliation(s)
- Konrad A Szychowski
- Department of Lifestyle Disorders and Regenerative Medicine, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszow, Poland
| | - Bartosz Skóra
- Department of Lifestyle Disorders and Regenerative Medicine, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszow, Poland
| | - Tadeusz Pomianek
- Department of Management, Faculty of Administration and Social Sciences, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszow, Poland
| | - Jan Gmiński
- Department of Lifestyle Disorders and Regenerative Medicine, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszow, Poland
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Blocking Effect of Chaga Mushroom (Inonotus oliquus) Extract for Immune Checkpoint CTLA-4/CD80 Interaction. APPLIED SCIENCES-BASEL 2020. [DOI: 10.3390/app10175774] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Inonotus obliquus, also known as the Chaga mushroom, has been used as a traditional medicine to treat many different diseases in Asia. Ethanol and water extraction were performed to examine the blocking effect of the Chaga mushroom on the CTLA-4/CD80 interaction. The inhibitory activities of the Chaga mushroom/70% EtOH extract (CME) and the Chaga mushroom/water extract (CMW) were confirmed using several cell-based assays. To identify the contents of major compounds CME and CMW, we performed HPLC analysis. The content of lanosterol (1) in CME was 0.41%. Our findings provide experimental evidence that the Chaga mushroom can develop a small-molecule inhibitor that blocks the CTLA-4/CD80 interaction.
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Sadowska A, Zapora E, Sawicka D, Niemirowicz-Laskowska K, Surażyński A, Sułkowska-Ziaja K, Kała K, Stocki M, Wołkowycki M, Bakier S, Pawlik A, Jaszek M, Muszyńska B, Car H. Heterobasidion annosum Induces Apoptosis in DLD-1 Cells and Decreases Colon Cancer Growth in In Vivo Model. Int J Mol Sci 2020; 21:ijms21103447. [PMID: 32414138 PMCID: PMC7279362 DOI: 10.3390/ijms21103447] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/07/2020] [Accepted: 05/09/2020] [Indexed: 12/20/2022] Open
Abstract
Application of substances from medicinal mushrooms is one of the interesting approaches to improve cancer therapy. In this study, we commenced a new attempt in the field of Heterobasidion annosum (Fr.) Bref. sensu lato to further extend our knowledge on this basidiomycete fungus. For this purpose, analysis of the active substances of Heterobasidion annosum methanolic extract and also its influence on colorectal cancer in terms of in vitro and in vivo experiments were performed. In vivo studies on mice were conducted to verify its acute toxicity and to further affirm its anticancer potential. Results indicated that all the most common substances of best known medicinal mushrooms that are also responsible for their biological activity are present in tested extracts. In vitro tests showed a high hemocompatibility and a significant decrease in viability and proliferation of DLD-1 cells in a concentration-dependent manner of Heterobasidion annosum extract. The studies performed on xenograft model of mice showed lower tendency of tumor growth in the group of mice receiving Heterobasidion annosum extract as well as mild or moderate toxicity. Obtained results suggest beneficial potential of Heterobasidion annosum against colon cancer as cytotoxic agent or as adjuvant anticancer therapy.
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Affiliation(s)
- Anna Sadowska
- Department of Experimental Pharmacology, Medical University of Białystok, Szpitalna 37, 15-295 Bialystok, Poland; (D.S.); (K.N.-L.); (H.C.)
- Correspondence: ; Tel.: +48-85-748-5554
| | - Ewa Zapora
- Institute of Forest Sciences, Bialystok University of Technology, Wiejska 45E, 15-351 Bialystok, Poland; (E.Z.); (M.S.); (M.W.); (S.B.)
| | - Diana Sawicka
- Department of Experimental Pharmacology, Medical University of Białystok, Szpitalna 37, 15-295 Bialystok, Poland; (D.S.); (K.N.-L.); (H.C.)
| | - Katarzyna Niemirowicz-Laskowska
- Department of Experimental Pharmacology, Medical University of Białystok, Szpitalna 37, 15-295 Bialystok, Poland; (D.S.); (K.N.-L.); (H.C.)
| | - Arkadiusz Surażyński
- Department of Medicinal Chemistry, Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok, Poland;
| | - Katarzyna Sułkowska-Ziaja
- Department of Pharmaceutical Botany, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland; (K.S.-Z.); (K.K.); (B.M.)
| | - Katarzyna Kała
- Department of Pharmaceutical Botany, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland; (K.S.-Z.); (K.K.); (B.M.)
| | - Marcin Stocki
- Institute of Forest Sciences, Bialystok University of Technology, Wiejska 45E, 15-351 Bialystok, Poland; (E.Z.); (M.S.); (M.W.); (S.B.)
| | - Marek Wołkowycki
- Institute of Forest Sciences, Bialystok University of Technology, Wiejska 45E, 15-351 Bialystok, Poland; (E.Z.); (M.S.); (M.W.); (S.B.)
| | - Sławomir Bakier
- Institute of Forest Sciences, Bialystok University of Technology, Wiejska 45E, 15-351 Bialystok, Poland; (E.Z.); (M.S.); (M.W.); (S.B.)
| | - Anna Pawlik
- Department of Biochemistry and Biotechnology, Maria Curie Sklodowska University, Akademicka 19, 20-033 Lublin, Poland; (A.P.); (M.J.)
| | - Magdalena Jaszek
- Department of Biochemistry and Biotechnology, Maria Curie Sklodowska University, Akademicka 19, 20-033 Lublin, Poland; (A.P.); (M.J.)
| | - Bożena Muszyńska
- Department of Pharmaceutical Botany, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland; (K.S.-Z.); (K.K.); (B.M.)
| | - Halina Car
- Department of Experimental Pharmacology, Medical University of Białystok, Szpitalna 37, 15-295 Bialystok, Poland; (D.S.); (K.N.-L.); (H.C.)
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Eid JI, Das B. Molecular insights and cell cycle assessment upon exposure to Chaga (Inonotus obliquus) mushroom polysaccharides in zebrafish (Danio rerio). Sci Rep 2020; 10:7406. [PMID: 32366825 PMCID: PMC7198532 DOI: 10.1038/s41598-020-64157-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 04/06/2020] [Indexed: 02/08/2023] Open
Abstract
Chaga (Inonotus obliquus) mushroom is considered as one of the most powerful antioxidants across the world. Though the therapeutic effects of Chaga components are well characterized in vitro, the in vivo developmental effects are not elucidated in detail. In this study, we assessed the in vivo developmental effects of Chaga polysaccharides in zebrafish, along with revealing the effects on cell cycle and apoptosis. Chaga mushroom polysaccharides comprised xylulose, rhamnose, mannose, glucose, inositol, and galactose, in addition to phenolic compounds; zebrafish embryos exhibited normal embryonic development upon transient exposure to Chaga extract (24 hours). Most embryos (>90%) were found to be healthy even at high concentrations (5 mg/mL). In addition, staining with the DNA binding dye, acridine orange showed that Chaga polysaccharides alleviated oxidative stress. Flow cytometric analysis using H2DCFDA that specifically binds to cells with fragmented DNA showed significantly reduced levels of intracellular reactive oxygen species (ROS) (p < 0.05), which in turn reduced apoptosis in the developing embryos. Cell cycle analysis by measuring the DNA content using flow cytometry revealed that Chaga polysaccharides moderately arrested the cells at G1 stage, thereby inhibiting cell proliferation that can be further explored in cancer studies. Overall, transient exposure of Chaga polysaccharide extract reduced intracellular ROS and assisted in the normal development of zebrafish.
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Affiliation(s)
- Jehane Ibrahim Eid
- Department of Zoology, Faculty of Science, Cairo University, Giza, 12613, Egypt.
| | - Biswadeep Das
- School of Biotechnology, KIIT University, Bhubaneswar, 751024, India
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25
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He MQ, Zhao RL, Hyde KD, Begerow D, Kemler M, Yurkov A, McKenzie EHC, Raspé O, Kakishima M, Sánchez-Ramírez S, Vellinga EC, Halling R, Papp V, Zmitrovich IV, Buyck B, Ertz D, Wijayawardene NN, Cui BK, Schoutteten N, Liu XZ, Li TH, Yao YJ, Zhu XY, Liu AQ, Li GJ, Zhang MZ, Ling ZL, Cao B, Antonín V, Boekhout T, da Silva BDB, De Crop E, Decock C, Dima B, Dutta AK, Fell JW, Geml J, Ghobad-Nejhad M, Giachini AJ, Gibertoni TB, Gorjón SP, Haelewaters D, He SH, Hodkinson BP, Horak E, Hoshino T, Justo A, Lim YW, Menolli N, Mešić A, Moncalvo JM, Mueller GM, Nagy LG, Nilsson RH, Noordeloos M, Nuytinck J, Orihara T, Ratchadawan C, Rajchenberg M, Silva-Filho AGS, Sulzbacher MA, Tkalčec Z, Valenzuela R, Verbeken A, Vizzini A, Wartchow F, Wei TZ, Weiß M, Zhao CL, Kirk PM. Notes, outline and divergence times of Basidiomycota. FUNGAL DIVERS 2019. [DOI: 10.1007/s13225-019-00435-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
AbstractThe Basidiomycota constitutes a major phylum of the kingdom Fungi and is second in species numbers to the Ascomycota. The present work provides an overview of all validly published, currently used basidiomycete genera to date in a single document. An outline of all genera of Basidiomycota is provided, which includes 1928 currently used genera names, with 1263 synonyms, which are distributed in 241 families, 68 orders, 18 classes and four subphyla. We provide brief notes for each accepted genus including information on classification, number of accepted species, type species, life mode, habitat, distribution, and sequence information. Furthermore, three phylogenetic analyses with combined LSU, SSU, 5.8s, rpb1, rpb2, and ef1 datasets for the subphyla Agaricomycotina, Pucciniomycotina and Ustilaginomycotina are conducted, respectively. Divergence time estimates are provided to the family level with 632 species from 62 orders, 168 families and 605 genera. Our study indicates that the divergence times of the subphyla in Basidiomycota are 406–430 Mya, classes are 211–383 Mya, and orders are 99–323 Mya, which are largely consistent with previous studies. In this study, all phylogenetically supported families were dated, with the families of Agaricomycotina diverging from 27–178 Mya, Pucciniomycotina from 85–222 Mya, and Ustilaginomycotina from 79–177 Mya. Divergence times as additional criterion in ranking provide additional evidence to resolve taxonomic problems in the Basidiomycota taxonomic system, and also provide a better understanding of their phylogeny and evolution.
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26
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Duru KC, Kovaleva EG, Danilova IG, Bijl P. The pharmacological potential and possible molecular mechanisms of action ofInonotus obliquusfrom preclinical studies. Phytother Res 2019; 33:1966-1980. [DOI: 10.1002/ptr.6384] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 03/19/2019] [Accepted: 04/15/2019] [Indexed: 12/21/2022]
Affiliation(s)
- Kingsley C. Duru
- Department of Technology for Organic SynthesisUral Federal University Yekaterinburg Russia
| | - Elena G. Kovaleva
- Department of Technology for Organic SynthesisUral Federal University Yekaterinburg Russia
| | - Irina G. Danilova
- Department of Technology for Organic SynthesisUral Federal University Yekaterinburg Russia
- Institute of Immunology and Physiology of the Ural BranchRussia Academy of Science Yekaterinburg Russia
| | - Pieter Bijl
- Department of Pharmacology, Faculty of Medicine and Health SciencesStellenbosch University Cape Town South Africa
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Khatua S, Chandra S, Acharya K. Expanding knowledge on Russula alatoreticula, a novel mushroom from tribal cuisine, with chemical and pharmaceutical relevance. Cytotechnology 2019; 71:245-259. [PMID: 30603923 PMCID: PMC6368521 DOI: 10.1007/s10616-018-0280-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Accepted: 11/08/2018] [Indexed: 12/31/2022] Open
Abstract
Since antiquity, numerous macrofungi are being worshiped as food and natural medicine especially in Asian tribal communities. Recent investigation has correlated these medicinal properties with bioactive components including phenols and flavonoids. However, research on mushrooms is not satisfactory; as several traditionally prized members remain undiscovered or poorly explored yet. This backdrop tempted us to unveil secondary metabolites empowered with therapeutics from an ethnic delicacy, Russula alatoreticula that was justified as a novel macrofungus in our previous publication. Accordingly, methanol extract was prepared from dried basidiocarps that was found to be enriched with phenolic compounds (pyrogallol > cinnamic acid > p-coumaric acid) and ascorbic acid. As a result, the fraction exhibited strong antioxidant activity evident by the ability of quenching free radicals, chelating Fe2+ ion and reducing components with EC50 of 263-2382 µg/ml. Besides, effective antibacterial potential against six investigated microbes was also noticed where MIC value ranged from 99 to 2673.74 µg/ml. Furthermore, the extract revealed promising anticancer property as it induced apoptosis of Hep3B cell (IC50 358.57 µg/ml) by imparting morphological changes, interfering cell cycle, depleting MMP and alleviating ROS through Bax, Bcl2, caspases 9 and 3 intrinsic mitochondrial pathway. Overall study implied that the immense bioactive potential of R. alatoreticula could possibly be utilized as a good source of natural supplement to combat against free radicals, pathogenic bacteria and hepatocellular carcinoma as well as in food safety industry.
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Affiliation(s)
- Somanjana Khatua
- Molecular and Applied Mycology and Plant Pathology Laboratory, Department of Botany, Centre of Advanced Study, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700019, West Bengal, India
| | - Swarnendu Chandra
- Molecular and Applied Mycology and Plant Pathology Laboratory, Department of Botany, Centre of Advanced Study, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700019, West Bengal, India
| | - Krishnendu Acharya
- Molecular and Applied Mycology and Plant Pathology Laboratory, Department of Botany, Centre of Advanced Study, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700019, West Bengal, India.
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28
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Gil YG, Kang S, Chae A, Kim YK, Min DH, Jang H. Synthesis of porous Pd nanoparticles by therapeutic chaga extract for highly efficient tri-modal cancer treatment. NANOSCALE 2018; 10:19810-19817. [PMID: 30334053 DOI: 10.1039/c8nr07172a] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Porous palladium nanoparticles were designed and synthesized to maximize the pharmacological activity of the chaga mushroom (Inonotus obliquus) extract, which has anticancer and antibacterial activities. In the present study, we synthesized anisotropic porous Pd nanostructures with ultraviolet-visible-near infrared whole wavelength region absorption using chaga extract concentration-dependent reductant-mediated synthesis. The porous Pd nanoparticles exhibited a surface chaga extract-derived anticancer effect, controlled delivery of doxorubicin through electrostatic interaction, and a photothermal conversion effect under 808 nm laser irradiation. The combined application of the three cancer treatment approaches clearly demonstrated the feasibility of synergistic tri-modal therapy. The present platform using Pd, which is a key constituent element of nanocatalysts but is not commonly used in biological applications, suggests numerous applications utilizing Pd nanostructures, as well as the potential development of new cancer therapies.
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Affiliation(s)
- Yeong-Gyu Gil
- Department of Chemistry, Kwangwoon University, 20, Gwangwoon-ro, Nowon-gu, Seoul 01897, Republic of Korea.
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Baek J, Roh HS, Baek KH, Lee S, Lee S, Song SS, Kim KH. Bioactivity-based analysis and chemical characterization of cytotoxic constituents from Chaga mushroom (Inonotus obliquus) that induce apoptosis in human lung adenocarcinoma cells. JOURNAL OF ETHNOPHARMACOLOGY 2018; 224:63-75. [PMID: 29800742 DOI: 10.1016/j.jep.2018.05.025] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 05/14/2018] [Accepted: 05/17/2018] [Indexed: 06/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Inonotus obliquus, also known as Chaga mushroom, is one of the most widely appreciated wild edible mushrooms in Russia and northern European countries and is renowned for its use in cancer treatment. Indeed, recently published in vitro and in vivo studies have demonstrated its anticancer activity in various types of cancer and support its potential application for therapeutic intervention in cancer. However, its activity against lung cancer, the most commonly diagnosed cancer and the leading cause of cancer death worldwide, and the underlying molecular basis of its action remain to be fully elucidated. OBJECTIVE This study aimed to evaluate the cytotoxic activity of I. obliquus in four human lung adenocarcinoma cell lines with different p53 status (A549, H1264, H1299, and Calu-6) and identify its active constituents by bioactivity-based analysis and the underlying molecular basis of their cytotoxicity on lung cancer cells. MATERIALS AND METHODS Bioactivity-guided fractionation and preparative/semi-preparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) were assessed using the WST-1 assay and TUNEL staining, respectively. Caspase activation was assessed by detecting its surrogate markers, cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3, using an immunoblot assay. RESULTS The MeOH extract of I. obliquus reduced cell viability in all lung cancer cell lines tested through induction of apoptosis accompanied by caspase-3 cleavage. Bioactivity-guided fractionation of the MeOH extract and chemical investigation of its cytotoxic hexane-soluble and CH2Cl2-soluble fractions led to the isolation of eight triterpenoids (1-8), including a new lanostane-type triterpenoid named chagabusone A (7). The structures of the isolates were elucidated based on spectroscopic analysis, including 1D and 2D NMR and high-resolution ESIMS. Among isolated compounds, compounds 1, 6, and 7 showed the most potent cytotoxic activity in all human lung cancer cell lines examined, with IC50 values ranging from 75.1 to 227.4 μM. Cytotoxicity of these compounds was mediated by apoptosis with caspase-3 activation. CONCLUSION These findings provide experimental evidence supporting the potential application of I. obliquus in lung cancer treatment and reveal the molecular basis underlying its cytotoxic activity against human lung cancer cells.
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Affiliation(s)
- Jiwon Baek
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
| | - Hyun-Soo Roh
- Department of Molecular and Cellular Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
| | - Kwan-Hyuck Baek
- Department of Molecular and Cellular Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
| | - Seulah Lee
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
| | - Seul Lee
- Department of Molecular and Cellular Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
| | - Seong-Soo Song
- Department of Molecular and Cellular Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
| | - Ki Hyun Kim
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
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Zeolite X from coal fly ash inhibits proliferation of human breast cancer cell lines (MCF-7) via induction of S phase arrest and apoptosis. Mol Biol Rep 2018; 45:2063-2074. [DOI: 10.1007/s11033-018-4363-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 09/05/2018] [Indexed: 12/31/2022]
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31
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Subhapriya S, Gomathipriya P. Induction of apoptotic effects of anti-proliferative zeolite X from coal fly ash on cervical cancer (HeLa) cell lines. Mol Biol Rep 2018; 45:1077-1087. [PMID: 30047039 DOI: 10.1007/s11033-018-4259-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Accepted: 07/12/2018] [Indexed: 12/12/2022]
Abstract
The synthesised zeolite X from coal fly ash showed significant cytotoxic activity in contradiction of HeLa cells (cervical cancer) in a concentration-dependent way at concentrations ranges from 200 µg to 0.781 µg/ml as shown by MTT assay and failed to cause cytotoxic effect in normal cells (Gh239). Cell cycle analysis exposed that zeolite X (10 and 15 µg/ml) endorses cell growth inhibition by inducing G2/M phase arrest in HeLa cells as observed using flow cytometry. The confocal microscopic results depicted increased early apoptotic related changes in HeLa cell lines induced by zeolite X at a dosage of 10, 15 and 20 µg/ml. Zeolite X at a dosage of 10, 15 and 20 µg/ml in HeLa cells showed fragmentation of DNA by ladder pattern thereby indicates that cell death is related with apoptosis. By the increase of Bax/Bcl-2 ratio, zeolite X leads to the caspase-3 and caspase-9 activation and allow the cells to enter apoptosis. These collective results evidently showed that the influence of mitochondria-mediated signalling pathway in zeolite X induced apoptosis and intensely delivered investigational suggestion for the use of zeolite X as a significant curative agent in the preclusion and therapy of human cervical carcinoma.
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Affiliation(s)
- S Subhapriya
- Department of Chemical Engineering, Anna University, A.C. Tech Campus, Chennai, Tamil Nadu, 600 025, India
| | - P Gomathipriya
- Department of Chemical Engineering, Anna University, A.C. Tech Campus, Chennai, Tamil Nadu, 600 025, India.
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Blagodatski A, Yatsunskaya M, Mikhailova V, Tiasto V, Kagansky A, Katanaev VL. Medicinal mushrooms as an attractive new source of natural compounds for future cancer therapy. Oncotarget 2018; 9:29259-29274. [PMID: 30018750 PMCID: PMC6044372 DOI: 10.18632/oncotarget.25660] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 06/04/2018] [Indexed: 02/07/2023] Open
Abstract
Medicinal mushrooms have been used throughout the history of mankind for treatment of various diseases including cancer. Nowadays they have been intensively studied in order to reveal the chemical nature and mechanisms of action of their biomedical capacity. Targeted treatment of cancer, non-harmful for healthy tissues, has become a desired goal in recent decades and compounds of fungal origin provide a vast reservoir of potential innovational drugs. Here, on example of four mushrooms common for use in Asian and Far Eastern folk medicine we demonstrate the complex and multilevel nature of their anticancer potential, basing upon different groups of compounds that can simultaneously target diverse biological processes relevant for cancer treatment, focusing on targeted approaches specific to malignant tissues. We show that some aspects of fungotherapy of tumors are studied relatively well, while others are still waiting to be fully unraveled. We also pay attention to the cancer types that are especially susceptible to the fungal treatments.
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Affiliation(s)
- Artem Blagodatski
- Centre for Genomic and Regenerative Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russian Federation.,Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland
| | - Margarita Yatsunskaya
- Federal Scientific Center of the East Asia Terrestrial Biodiversity FEB RAS, Vladivostok, Russia
| | - Valeriia Mikhailova
- Centre for Genomic and Regenerative Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russian Federation
| | - Vladlena Tiasto
- Centre for Genomic and Regenerative Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russian Federation
| | - Alexander Kagansky
- Centre for Genomic and Regenerative Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russian Federation
| | - Vladimir L Katanaev
- Centre for Genomic and Regenerative Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russian Federation.,Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland
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Géry A, Dubreule C, André V, Rioult JP, Bouchart V, Heutte N, Eldin de Pécoulas P, Krivomaz T, Garon D. Chaga ( Inonotus obliquus), a Future Potential Medicinal Fungus in Oncology? A Chemical Study and a Comparison of the Cytotoxicity Against Human Lung Adenocarcinoma Cells (A549) and Human Bronchial Epithelial Cells (BEAS-2B). Integr Cancer Ther 2018; 17:832-843. [PMID: 29484963 PMCID: PMC6142110 DOI: 10.1177/1534735418757912] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Background:Inonotus obliquus, also known as Chaga, is a parasitic fungus
growing on birches and used in traditional medicine (especially by Khanty
people) to treat various health problems. In this study, we aimed to quantify
the 3 metabolites frequently cited in literature, that is, betulin, betulinic
acid, and inotodiol in the Chaga recently discovered in forests located in
Normandy (France), and to compare their concentrations with Ukrainian and
Canadian Chaga. This study also explores the cytotoxicity of the French Chaga
against cancer-derived cells and transformed cells. Methods: A
quantification method by HPLC-MS-MS (high-performance liquid
chromatography–tandem mass spectrometry) of betulin, betulinic acid, and
inotodiol was developed to study the French Chaga and compare the concentration
of these metabolites with extracts provided from Chaga growing in Canada and
Ukraine. This method was also used to identify and quantify those 3 compounds in
other traditional preparations of Chaga (aqueous extract, infusion, and
decoction). Among these preparations, the aqueous extract that contains betulin,
betulinic acid, and inotodiol was chosen to evaluate and compare its cytotoxic
activity toward human lung adenocarcinoma cells (A549 line) and human bronchial
epithelial cells (BEAS-2B line). Results: French Chaga contains
betulin and betulinic acid at higher levels than in other Chaga, whereas the
concentration of inotodiol is greater in the Canadian Chaga. Moreover, the
results highlighted a cytotoxic activity of the Chaga’s aqueous extract after 48
and 72 hours of exposure with a higher effect on cancer-derived cells A549 than
on normal transformed cells BEAS-2B (P = 0.025 after 48 hours
of exposure and P = 0.004 after 72 hours of exposure).
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Affiliation(s)
- Antoine Géry
- 1 Normandie University, UNICAEN, Centre F. Baclesse, Caen, France
| | | | - Véronique André
- 1 Normandie University, UNICAEN, Centre F. Baclesse, Caen, France
| | | | | | | | | | - Tetyana Krivomaz
- 4 National University of Architecture and Construction, Kyiv, Ukraine
| | - David Garon
- 1 Normandie University, UNICAEN, Centre F. Baclesse, Caen, France
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Patel S, Rauf A, Khan H. The relevance of folkloric usage of plant galls as medicines: Finding the scientific rationale. Biomed Pharmacother 2018; 97:240-247. [PMID: 29091872 DOI: 10.1016/j.biopha.2017.10.111] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 10/17/2017] [Accepted: 10/21/2017] [Indexed: 10/18/2022] Open
Abstract
Galls, the abnormal growths in plants, induced by virus, bacteria, fungi, nematodes, arthropods, or even other plants, are akin to cancers in fauna. The galls which occur in a myriad of forms are phytochemically-distinct from the normal plant tissues, for these are the sites of tug-of-war, just like the granuloma in animals. To counter the stressors, in the form of the effector proteins of the invaders, the host plants elaborate a large repertoire of metabolites, which they normally will not produce. Perturbation of the jasmonic acid pathway, and the overexpression of auxin, and cytokinin, promote the tissue proliferation and the resultant galls. Though the plant family characteristics and the attackers determine the gall biochemistry, most of the galls are rich in bioactive phytochemicals such as phenolic acids, anthocyanins, purpurogallin, flavonoids, tannins, steroids, triterpenes, alkaloids, lipophilic components (tanshinone) etc. Throughout the long trajectory of evolution, humans have learned to use the galls as therapeutics, much like other plant parts. In diverse cultures, the evidence of folkloric usage of galls abound. Among others, galls from the plant genus like Rhus, Pistacia, Quercus, Terminalia etc. are popular as ethnomedicine. This review mines the literature on galling agents, and the medicinal relevance of galls.
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Affiliation(s)
- Seema Patel
- Bioinformatics and Medical Informatics Research Center, San Diego State University, San Diego, 92182, USA.
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar, 23561, K.P.K, Pakistan
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan, 23200, Pakistan
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Tsai CC, Li YS, Lin PP. Inonotus obliquus extract induces apoptosis in the human colorectal carcinoma’s HCT-116 cell line. Biomed Pharmacother 2017; 96:1119-1126. [DOI: 10.1016/j.biopha.2017.11.111] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Revised: 11/19/2017] [Accepted: 11/20/2017] [Indexed: 01/01/2023] Open
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Staniszewska J, Szymański M, Ignatowicz E. Antitumor and immunomodulatory activity of Inonotus obliquus. HERBA POLONICA 2017. [DOI: 10.1515/hepo-2017-0013] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Summary
The article presents the antitumor and immunomodulatory activity of compounds and extracts from Inonotus obliquus. Polysaccharides isolated from sclerotium have a direct antitumor effect due to protein synthesis inhibition in tumor cells. Polysaccharides derived from the mycelium function by activating the immune system. Due to the limited toxicity of these substances, both extracts as well as isolated and purified chemicals may be a good alternative to current chemotherapy and play a role in cancer prevention. In vitro experiments have shown the inhibition of inflammation with the influence of action of I. obliquus extracts; however, in vivo experiments on animals implanted with tumor cells of different types have shown the activation of the host immune system. This led to decrease in tumor mass and prolonged survival. The immunomodulatory mechanism of action is complex and it seems that stimulation of macrophages and induction of apoptosis in cancer cells is of great importance.
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Affiliation(s)
- Justyna Staniszewska
- Department of Pharmacognosy Poznan , University of Medical Sciences , Święcickiego 4, 60–781 Poznań , Poland
| | - Marcin Szymański
- Department of Pharmacognosy Poznan , University of Medical Sciences , Święcickiego 4, 60–781 Poznań , Poland
| | - Ewa Ignatowicz
- Department of Pharmaceutical Biochemistry , Poznan University of Medical Sciences , Święcickiego 4, 60–781 Poznań , Poland
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Lee MS, Kim MS, Yoo JK, Lee JY, Ju JE, Jeong YK. Enhanced anticancer effects of a mixture of low-dose mushrooms and Panax ginseng root extracts in human colorectal cancer cells. Oncol Rep 2017; 38:1597-1604. [PMID: 28714027 DOI: 10.3892/or.2017.5796] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 06/30/2017] [Indexed: 11/05/2022] Open
Abstract
Worldwide, colorectal cancer is the third most common cancer in men and the second most common in women. As conventional colorectal cancer therapies result in various side effects, there is a need for adjuvant therapy that can enhance the conventional therapies without complications. In this study, we investigated the anticancer effects of combined mixture of the several medicinal mushrooms and Panax ginseng root extracts (also called Amex7) as an adjuvant compound in the treatment of human colorectal cancer. We observed the in vivo inhibitory effect of Amex7 (1.25, 6.25, and 12.5 ml/kg, oral administration, twice daily) on tumor growth in a mouse model xenografted with HT-29 human colorectal cancer cells. In vitro, at 6, 12, and 24 h after 4% Amex7 treatment, we analyzed cell cycle by flow cytometry and the expression levels of cell cycle progression, apoptosis, and DNA damage repair-related proteins using immunoblotting and immunofluorescence staining in HT-29 cell line. As a result, Amex7 significantly suppressed tumor growth in HT-29 human colorectal cancer cells and xenografts. In vitro, Amex7 induced G2/M arrest through the regulation of cell cycle proteins and cell death by apoptosis and autophagy. Additionally, Amex7 consistently induced DNA damage and delayed the repair of Amex7-induced DNA damage by reducing the level of HR repair proteins. In conclusion, Amex7 enhanced anticancer effects through the induction of G2/M arrest and cell death, including apoptosis and autophagy. Furthermore, Amex7 impaired DNA damage repair. The present study provides a scientific rationale for the clinical use of a combined mixture of medicinal mushrooms and P. ginseng root extracts as an adjuvant treatment in human colorectal cancer.
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Affiliation(s)
- Mi So Lee
- Radiation Non-clinical Center, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea
| | - Mi-Sook Kim
- Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea
| | - Jae Kuk Yoo
- Han Kook Shin Yak Pharmaceutical Co., Ltd., Nonsan 33023, Republic of Korea
| | - Ji Young Lee
- Radiation Non-clinical Center, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea
| | - Jae Eun Ju
- Radiation Non-clinical Center, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea
| | - Youn Kyoung Jeong
- Radiation Non-clinical Center, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea
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Nikitina SA, Khabibrakhmanova VR, Sysoeva MA. [Composition and biological activity of triterpenes and steroids from Inonotus obliquus (chaga)]. BIOMEDIT︠S︡INSKAI︠A︡ KHIMII︠A︡ 2017; 62:369-75. [PMID: 27562990 DOI: 10.18097/pbmc20166204369] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Data on the chemical composition of triterpenic and steroid compounds, isolated from the chaga mushroom grown in natural environment or in a synthetic culture have been summarized. Special attention has been paid to the biological activity of chaga mushroom extracts and these particular compounds against various cancer cell lines in vitro and in vivo. This analysis has demonstrated some common features in inhibition of growth of various cell lines by chaga mushroom components. In this context, the most active are triterpene compounds containing OH group at C-22 and a side chain unsaturated bond.
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Affiliation(s)
- S A Nikitina
- Kazan National Research Technological University, Kazan, Russia
| | | | - M A Sysoeva
- Kazan National Research Technological University, Kazan, Russia
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Smolibowska J, Szymański M, Szymański A. Medicinal properties of fungi occurring on Betula sp. trees. A review. HERBA POLONICA 2016. [DOI: 10.1515/hepo-2016-0018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Summary
The article presents the chemical costituents and pharmacological properties of polyporoid fungi found on birch, namely Piptoporus betulinus, Inonotus obliquus, Lenzites betulina, Fomes fomentarius, and Trametes versicolor. The in vitro and in vivo studies on the effect of different extracts from above-mentioned fungi on the human organism shown anti-cancer, anti-inflammatory, antiviral, antibacterial and immunostimulant activity, conditioned by the presence of such compounds as polysaccharides, polyphenols or terpenes. These fungi are commonly found in Poland and may superbly compete with Ganoderma lucidum (Reishi) or Lentinula edodes (Shitake) used in Asia for medicinal purposes.
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Affiliation(s)
- Joanna Smolibowska
- Department of Pharmacognosy, Poznan University of Medical Sciences, Święcickiego 4, 60–781 Poznań, Poland
| | - Marcin Szymański
- Department of Pharmacognosy, Poznan University of Medical Sciences, Święcickiego 4, 60–781 Poznań, Poland
| | - Arkadiusz Szymański
- Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89, 61-614 Poznań, Poland
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Lin X, Wei J, Chen Y, He P, Lin J, Tan S, Nie J, Lu S, He M, Lu Z, Huang Q. Isoorientin from Gypsophila elegans induces apoptosis in liver cancer cells via mitochondrial-mediated pathway. JOURNAL OF ETHNOPHARMACOLOGY 2016; 187:187-194. [PMID: 27130644 DOI: 10.1016/j.jep.2016.04.050] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/24/2015] [Revised: 04/12/2016] [Accepted: 04/26/2016] [Indexed: 06/05/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Gypsophila elegans has been used as a traditional herbal medicine for treating immune disorders and chronic liver diseases in China. The aim of this study is to isolate an active ingredient from this herb and investigate its anti-tumor activity. MATERIALS AND METHODS An active ingredient was isolated from the ethanol extract using bioassay-guided screening. And its anti-tumor activity was analyzed by testing the cytotoxicity, lactate dehydrogenase (LDH) release, clonogenecity and migration in HepG2 cells. To investigate its potential mechanism, cell apoptosis, cell cycle arrest, reactive oxygen species (ROS), cytochrome c, mitochondria membrane potential (MMP) and caspase level were determined in liver cancer cell line HepG2. RESULTS A flavonoid glycoside, i.e., G. elegans isoorientin (GEI), was isolated from this herb and identified as Isoorientin-2″-O-α-l-arabinopyranosyl. Our results showed that GEI significantly inhibited the viability and proliferation of HepG2 cells in a dose- and time-dependent manner, and its cytotoxic effect was also confirmed by the elevated level of LDH. GEI treatment could markedly inhibit the clonogenicity and migration of HepG2 cells. Moreover, GEI induced remarkable apoptotic death of HepG2 cells through cell cycle arrest at G1 phase via the regulation of cell cycle-related genes, such as cyclin D, cyclin E and CDK2. Further study showed that GEI treatment significantly elevated ROS formation, followed by attenuation of MMP via up-regulation of Bax and down-regulation of Bcl-2, accompanied by cytochrome c release to the cytosol. In addition, GEI treatment resulted in a significant dose-dependent increase in caspase-3 and -9 proteolytic activities. CONCLUSION The present study demonstrates that the ability of GEI to induce apoptosis against HepG2 cells mediated by mitochondrial-mediated pathway.
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Affiliation(s)
- Xing Lin
- Guangxi Medical University, Nanning 530021, China
| | - Jinbin Wei
- Guangxi Medical University, Nanning 530021, China
| | - Yongxin Chen
- Guangxi Medical University, Nanning 530021, China; The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China
| | - Ping He
- Guangxi Medical University, Nanning 530021, China
| | - Jun Lin
- Guangxi Medical University, Nanning 530021, China
| | - Shimei Tan
- Guangxi Medical University, Nanning 530021, China
| | - Jinlan Nie
- Guangxi Medical University, Nanning 530021, China
| | - Shengjuan Lu
- Guangxi Medical University, Nanning 530021, China
| | - Min He
- Guangxi Medical University, Nanning 530021, China
| | - Zhongpeng Lu
- The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China; Department of Biochemistry, University of Arkansas Medical School, 4301 W. Markham, Little Rock, AR 72205-7199, USA
| | - Quanfang Huang
- The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
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Nikitina SA, Habibrakhmanova VR, Sysoeva MA. Chemical composition and biological activity of triterpenes and steroids of chaga mushroom. BIOCHEMISTRY (MOSCOW) SUPPLEMENT SERIES B: BIOMEDICAL CHEMISTRY 2016. [DOI: 10.1134/s1990750816010108] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Ju HM, Yu KW, Cho SD, Cheong SH, Kwon KH. Anti-cancer effects of traditional Korean wild vegetables in complementary and alternative medicine. Complement Ther Med 2016; 24:47-54. [DOI: 10.1016/j.ctim.2015.11.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Revised: 07/18/2015] [Accepted: 11/26/2015] [Indexed: 11/16/2022] Open
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Lan Z, Chong Z, Liu C, Feng D, Fang D, Zang W, Zhou J. Amantadine inhibits cellular proliferation and induces the apoptosis of hepatocellular cancer cells in vitro. Int J Mol Med 2015. [PMID: 26201988 DOI: 10.3892/ijmm.2015.2289] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies worldwide, and its incidence associated with viral infection has increased in recent years. Amantadine is a tricyclic symmetric amine that can effectively protect against the hepatitis C virus. However, its antitumor properties remain unclear. In the present study, the effects of amantadine on tumor cell viability, cell cycle regulation and apoptosis were investigated. The growth of HepG2 and SMMC‑7721 cells (HCC cell lines) was detected by an MTT assay. Flow cytometry was used to investigate cell cycle regulation and apoptosis. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were also performed to examine the expression of cell cycle‑ and apoptosis‑related genes and proteins, including cyclin E, cyclin D1, cyclin‑dependent kinase 2 (CDK2), B‑cell lymphoma 2 (Bcl‑2) and Bax. Our results demonstrated that amantadine markedly inhibited the proliferation of HepG2 and SMMC‑7721 cells in a dose‑ and time‑dependent manner and arrested the cell cycle at the G0/G1 phase. The levels of the cell cycle‑related genes and proteins (cyclin D1, cyclin E and CDK2) were reduced by amantadine, and apoptosis was significantly induced. Amantadine treatment also reduced Bcl‑2 and increased the Bax protein and mRNA levels. Additionally, Bcl‑2/Bax ratios were lower in the two HCC cell lines following amantadine treatment. Collectively, these results emphasize the role of amantadine in suppressing proliferation and inducing apoptosis in HCC cells, advocating its use as a novel tumor-suppressive therapeutic candidate.
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Affiliation(s)
- Zengmei Lan
- Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
| | - Zhaoyang Chong
- Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
| | - Cong Liu
- Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
| | - Danyang Feng
- Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
| | - Dihai Fang
- Department of Cardiology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
| | - Weijin Zang
- Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
| | - Jun Zhou
- Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
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Lee HS, Kim EJ, Kim SH. Ethanol extract of Innotus obliquus (Chaga mushroom) induces G1 cell cycle arrest in HT-29 human colon cancer cells. Nutr Res Pract 2015; 9:111-6. [PMID: 25861415 PMCID: PMC4388940 DOI: 10.4162/nrp.2015.9.2.111] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Revised: 10/20/2014] [Accepted: 10/21/2014] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND/OBJECTIVES Inonotus obliquus (I. obliquus, Chaga mushroom) has long been used as a folk medicine to treat cancer. In the present study, we examined whether or not ethanol extract of I. obliquus (EEIO) inhibits cell cycle progression in HT-29 human colon cancer cells, in addition to its mechanism of action. MATERIALS/METHODS To examine the effects of Inonotus obliquus on the cell cycle progression and the molecular mechanism in colon cancer cells, HT-29 human colon cancer cells were cultured in the presence of 2.5 - 10 µg/mL of EEIO, and analyzed the cell cycle arrest by flow cytometry and the cell cycle controlling protein expression by Western blotting. RESULTS Treatment cells with 2.5 - 10 µg/mL of EEIO reduced viable HT-29 cell numbers and DNA synthesis, increased the percentage of cells in G1 phase, decreased protein expression of CDK2, CDK4, and cyclin D1, increased expression of p21, p27, and p53, and inhibited phosphorylation of Rb and E2F1 expression. Among I. obliquus fractions, fraction 2 (fractionated by dichloromethane from EEIO) showed the same effect as EEIO treatment on cell proliferation and cell cycle-related protein levels. CONCLUSIONS These results demonstrate that fraction 2 is the major fraction that induces G1 arrest and inhibits cell proliferation, suggesting I. obliquus could be used as a natural anti-cancer ingredient in the food and/or pharmaceutical industry.
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Affiliation(s)
- Hyun Sook Lee
- Department of Food Science and Nutrition, Dongseo University, Busan 617-716, Korea
| | - Eun Ji Kim
- Research Institute, Adbiotech Co. Ltd., Gangwon 200-957, Korea
| | - Sun Hyo Kim
- Department of Technology and Home Economics Education, Kongju National University, 56 Kongjudaehak-ro, Chungnam 314-701, Korea
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Zhao LW, Zhong XH, Yang SY, Zhang YZ, Yang NJ. Inotodiol Inhabits Proliferation and Induces Apoptosis through Modulating Expression of cyclinE, p27, bcl-2, and bax in Human Cervical Cancer HeLa Cells. Asian Pac J Cancer Prev 2014; 15:3195-9. [DOI: 10.7314/apjcp.2014.15.7.3195] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Song FQ, Liu Y, Kong XS, Chang W, Song G. Progress on understanding the anticancer mechanisms of medicinal mushroom: inonotus obliquus. Asian Pac J Cancer Prev 2014; 14:1571-8. [PMID: 23679238 DOI: 10.7314/apjcp.2013.14.3.1571] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Cancer is a leading cause of death worldwide. Recently, the demand for more effective and safer therapeutic agents for the chemoprevention of human cancer has increased. As a white rot fungus, Inonotus obliquus is valued as an edible and medicinal resource. Chemical investigations have shown that I. obliquus produces a diverse range of secondary metabolites, including phenolic compounds, melanins, and lanostane-type triterpenoids. Among these are active components for antioxidant, antitumoral, and antiviral activities and for improving human immunity against infection of pathogenic microbes. Importantly, their anticancer activities have become a hot recently, but with relatively little knowledge of their modes of action. Some compounds extracted from I. obliquus arrest cancer cells in the G0/G1 phase and then induce cell apoptosis or differentiation, whereas some examples directly participate in the cell apoptosis pathway. In other cases, polysaccharides from I. obliquus can indirectly be involved in anticancer processes mainly via stimulating the immune system. Furthermore, the antioxidative ability of I. obliquus extracts can prevent generation of cancer cells. In this review, we highlight recent findings regarding mechanisms underlying the anticancer influence of I. obliquus, to provide a comprehensive landscape view of the actions of this mushroom in preventing cancer.
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Affiliation(s)
- Fu-Qiang Song
- Key Laboratory of Microbiology, Life Science College, Heilongjiang University, Harbin, China.
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Mishra S, Kang JH, Song KH, Park M, Kim DK, Park YJ, Choi C, Kim H, Kim M, Oh S. Inonotus Obliquus Suppresses Proliferation of Colorectal Cancer Cells and Tumor Growth in Mice Models by Downregulation of β-Catenin/NF-κB-Signaling Pathways. EUR J INFLAMM 2013. [DOI: 10.1177/1721727x1301100306] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Chaga mushroom (Inonotus obliquas) has been used as a folk remedy for several illnesses including gastrointestinal disorders. We recently reported the potent anti-inflammatory effect of chaga extract in experimental colitis. However, its effects on colorectal cancer (CRC) have not been clearly elucidated. We investigated the effects of an aqueous extract of Inonotus obliquus (IOAE) in vitro in HCT116 and DLD1 cell lines and in vivo for adenoma in APCMin/+ mice and colitis-associated colon cancer in AOM/DSS-treated mice. Results show that IOAE suppressed the proliferation of both cell lines, and inhibited the growth of intestinal polyps in APCMin/+ and colon tumors in AOM/DSS-treated mice. IOAE induced mitochondrial intrinsic pathway of apoptosis, autophagy, and S phase cell cycle arrest. IOAE suppressed the expression levels of iNOS and Cox-2 and mRNA levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-a and IFN-γ) in the intestine of mice models. IOAE suppressed the nuclear levels of β-catenin and inhibited its downstream targets (cyclin D1 and c-Myc) along with CRC oncogene CDK8. IOAE inhibited the expression of NF-κB at cytoplasmic and nuclear levels. Our results demonstrate that IOAE possess potent anti-inflammatory and anti-proliferative properties through downregulation of Wnt/β-catenin and NF-κB pathways. Considering recent anticancer approaches involving natural products with minimal side effects, we advocate that Inonotus obliquus could be a beneficial supplement in prevention of colorectal cancer.
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Affiliation(s)
- S.K. Mishra
- Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, Republic of Korea
| | - J-H. Kang
- Department of Food and Nutrition, Division of Natural Sciences, Chung-Ang University, Ansung, Republic of Korea
- Division of Cancer Biology, National Cancer Center, Goyang-si, Republic of Korea
| | - K-H. Song
- Division of Cancer Biology, National Cancer Center, Goyang-si, Republic of Korea
| | - M.S. Park
- Animal Science Branch, National Cancer Center, Goyang-si, Republic of Korea
| | - D-K. Kim
- Animal Science Branch, National Cancer Center, Goyang-si, Republic of Korea
| | - Y-J. Park
- Animal Science Branch, National Cancer Center, Goyang-si, Republic of Korea
| | - C. Choi
- Department of Food and Nutrition, Division of Natural Sciences, Chung-Ang University, Ansung, Republic of Korea
| | - H.M. Kim
- Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, Republic of Korea
| | - M.K. Kim
- Carcinogenesis Branch, Division of Cancer Epidemiology and Prevention, National Cancer Center, Goyang-si, Republic of Korea
| | - S.H. Oh
- Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, Republic of Korea
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Bak Y, Ham S, Baatartsogt O, Jung SH, Choi KD, Han TY, Han IY, Yoon DY. A1E inhibits proliferation and induces apoptosis in NCI-H460 lung cancer cells via extrinsic and intrinsic pathways. Mol Biol Rep 2013; 40:4507-19. [DOI: 10.1007/s11033-013-2544-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2012] [Accepted: 04/29/2013] [Indexed: 10/26/2022]
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Yoon TJ, Lee SJ, Kim EY, Cho EH, Kang TB, Yu KW, Suh HJ. Inhibitory effect of chaga mushroom extract on compound 48/80-induced anaphylactic shock and IgE production in mice. Int Immunopharmacol 2013; 15:666-70. [DOI: 10.1016/j.intimp.2013.03.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2013] [Revised: 03/03/2013] [Accepted: 03/15/2013] [Indexed: 12/13/2022]
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Ma L, Chen H, Dong P, Lu X. Anti-inflammatory and anticancer activities of extracts and compounds from the mushroom Inonotus obliquus. Food Chem 2013; 139:503-8. [PMID: 23561137 DOI: 10.1016/j.foodchem.2013.01.030] [Citation(s) in RCA: 156] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2012] [Revised: 12/29/2012] [Accepted: 01/05/2013] [Indexed: 01/05/2023]
Abstract
Mushroom Inonotus obliquus (I. obliquus) has been used as functional food and traditional Chinese herbs for long time. An efficient method for bioassay-guided preparative isolation was used for identifying the anti-inflammatory and anticancer constituents in I. obliquus. The petroleum ether and ethyl acetate fractions were found to have significant inhibition effects on NO production and NF-κB luciferase activity in macrophage RAW 264.7 cells and cytotoxicity against human prostatic carcinoma cell PC3 and breast carcinoma cell MDA-MB-231. Six main constituents were isolated from these two fractions and they were identified as lanosterol (1), 3β-hydroxy-8,24-dien-21-al (2), ergosterol (3), inotodiol (4), ergosterol peroxide (5) and trametenolic acid (6). Compound ergosterol, ergosterol peroxide and trametenolic acid showed anti-inflammatory activities and ergosterol peroxide and trametenolic acid showed obviously cytotoxicity on human prostatic carcinoma cell PC3 and breast carcinoma MDA-MB-231 cell. The results obtained in this work might contribute to understanding the biological activity of mushroom I. obliquus for food and drug application.
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Affiliation(s)
- Lishuai Ma
- Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China
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