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標題: Flavokawain B, a novel chalcone from Alpinia pricei Hayata with potent apoptotic activity: Involvement of ROS and GADD153 upstream of mitochondria-dependent apoptosis in HCT116 cells
作者: Kuo, Y.F.
Su, Y.Z.
Tseng, Y.H.
Wang, S.Y.
Wang, H.M.
Chueh, P.J.
關鍵字: Apoptosis;Alpinia pricei Hayata;Anticancer;Flavonoid;Flavokawain B;GADD153;ROS;Free radicals;endoplasmic-reticulum stress;unfolded protein response;bladder-cancer;cells;cycle arrest;mediated apoptosis;triggers apoptosis;up-regulation;colon-cancer;er stress;p38 mapk
Project: Free Radical Biology and Medicine
期刊/報告no:: Free Radical Biology and Medicine, Volume 49, Issue 2, Page(s) 214-226.
Flavonoids synthesized from chalcone precursors in plants have been shown to possess cytotoxic activities with therapeutic potential. We have isolated the novel chalcone flavokawain B from Alpinia pricei Hayata, a plant native to Taiwan that is used in food and traditional Chinese medicine. Here, we report for the first time that flavokawain B significantly inhibits the growth of colon cancer cells and provide novel insight into the molecular mechanisms that underlie its apoptotic activity. Flavokawain B exerts its apoptotic action through ROS generation and GADD153 up-regulation, which lead to mitochondria-dependent apoptosis characterized by release of cytochrome c and translocation of Bak. The up-regulation of GADD153 in flavokawain B-treated HCT116 cells is associated with mitochondrial dysfunction and altered expression of Bcl-2 family members. Moreover, pretreatment with the ROS scavenger N-acetylcysteine abolishes flavokawain B-induced ROS generation, GADD153 up-regulation, and apoptosis. Similarly, RNAi-mediated gene silencing reduced flavokawain B-enhanced expression of GADD153 and apoptotic Bim, leading to diminished apoptosis. Interestingly, flavokawain B provokes G2/M accumulation as well as autophagy, in addition to apoptosis, suggesting that multiple pathways are activated in flavokawain B-mediated anticancer activity. Taken together, our data provide evidence for a molecular mechanism to explain the apoptotic activity of Alpinia plants, showing that flavokawain B acts through ROS generation and GADD153 up-regulation to regulate the expression of Bcl-2 family members, thereby inducing mitochondrial dysfunction and apoptosis in HCT116 cells. (C) 2010 Elsevier Inc. All rights reserved.
ISSN: 0891-5849
DOI: 10.1016/j.freeradbiomed.2010.04.005
Appears in Collections:生物醫學研究所

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