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Title: Anti-cancer mechanisms of indirubin-3'-monoxime
Authors: SHI JIE
Keywords: indirubin-3'-monoxime; death receptor; Bid; Bax; Apoptosis
Issue Date: 28-Apr-2008
Citation: SHI JIE (2008-04-28). Anti-cancer mechanisms of indirubin-3'-monoxime. ScholarBank@NUS Repository.
Abstract: Indirubin-3b -monoxime (I3M) is a derivative of indirubin, an active component from a Chinese medicinal recipe with known anti-cancer function. In this study, we focused on the molecular mechanism underlying I3M-induced apoptosis, especially the critical role of the pro-apoptosis Bcl-2 family members. We first observed I3M-induced apoptosis in a time- and dose-dependent manner in three different types of human cancer cells. Induction of the caspase cascade for both the extrinsic and intrinsic pathways was demonstrated. Initiation of the death receptor pathway started with enhanced surface expression and protein level of DR4 and DR5, which correlated with the up-regulation of p53 and its transcriptional activity. Importantly, in HeLa cells caspase-8 activation resulted in Bid cleavage, followed by Bax conformational change. Consistently, stable knockdown of Bid abrogated I3M-induced Bax conformational change and cell death. Moreover, ectopic expression of a viral caspase inhibitor or Bcl-2 partially protected I3M-induced apoptosis.
Appears in Collections:Master's Theses (Open)

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