| Antcin B and its Ester Derivative from Antrodia camphorata Induce Apoptosis in Hepatocellular Carcinoma Cells Involves Enhancing Oxidative Stress Coincident with Activation of Intrinsic and Extrinsic Apoptotic Pathway. | |
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MedLine Citation:
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PMID: 21916504 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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ABSTRACT: The triterpenoids methylantcinate B (MAB) and antcin B (AB) isolated from the medicinal mushroom Antrodia camphorata has been identified as strong cytotoxic agents against various type of cancer cells, however, the mechanisms of MAB and AB-induced cytotoxicity have not been adequately explored. This study investigated the roles of caspase cascades, ROS, DNA damage, mitochondrial disruption, and Bax and Bcl-2 proteins in MAB and AB-induced apoptosis of hepatocellular carcinoma (HCC) HepG2 cells. Here, we showed that MAB and AB induced apoptosis in HepG2 cells, as characterized by increased DNA fragmentation, cleavage of PARP, sub-G1 population, chromatin condensation, loss of mitochondrial membrane potential and release of cytochrome c. Increasing the levels of caspase-2, -3, -8, and -9 activities was involved in MAB and AB-induced apoptosis, and they could be attenuated by inhibitors of specific caspases, indicating that MAB and AB triggered caspase-dependent apoptotic pathway. Additionally, the enhanced apoptotic effect correlates with high expression of Fas, Fas ligand as well as Bax and decreased protein levels of Bcl-XL and Bcl-2, suggesting that both the extrinsic and intrinsic apoptosis pathways were involved in the apoptotic processes. Incubation of HepG2 cells with antioxidant enzymes superoxide dismutase, catalase and, antioxidants N-acetylcysteine and ascorbic acid attenuated the ROS generation and apoptosis induced by MAB and AB, which indicate that ROS plays a pivotal role in cell death. NADPH oxidase activation was observed in MAB- and AB-stimulated HepG2 cells; however, inhibition of such activation by diphenylamine significantly blocked MAB and AB-induced ROS production and increased cell viability. Taken together, our results provide the first evidence that triterpenoids MAB and AB induced a NADPH oxidase-provoked oxidative stress and extrinsic and intrinsic apoptosis as a critical mechanism of cause cell death in HCC cells. |
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Authors:
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Yun-Chih Hsieh; Yerra Koteswara Rao; Jacqueline Whang-Peng; Chi-Ying F Huang; Song-Kun Shyue; Shi-Lan Hsu; Yew-Min Tzeng |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-14 |
Journal Detail:
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Title: Journal of agricultural and food chemistry Volume: - ISSN: 1520-5118 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0374755 Medline TA: J Agric Food Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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