Document Detail

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.
MedLine Citation:
PMID:  21916504     Owner:  NLM     Status:  Publisher    
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.
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:
Type:  JOURNAL ARTICLE     Date:  2011-9-14
Journal Detail:
Title:  Journal of agricultural and food chemistry     Volume:  -     ISSN:  1520-5118     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374755     Medline TA:  J Agric Food Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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