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https://doi.org/10.1016/j.bcp.2008.01.021
Title: | Critical role of Bid and Bax in indirubin-3′-monoxime-induced apoptosis in human cancer cells | Authors: | Shi, J. Shen, H.-M. |
Keywords: | Apoptosis Bax Bid Death receptor Indirubin-3′-monoxime |
Issue Date: | 1-May-2008 | Citation: | Shi, J., Shen, H.-M. (2008-05-01). Critical role of Bid and Bax in indirubin-3′-monoxime-induced apoptosis in human cancer cells. Biochemical Pharmacology 75 (9) : 1729-1742. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bcp.2008.01.021 | Abstract: | Indirubin-3′-monoxime (I3M) is a derivative of indirubin, an active component from a Chinese medicinal recipe with known anti-cancer function. I3M has been well established as a cyclin-dependent kinase (CDK) inhibitor, while the molecular mechanism underlying I3M-induced apoptosis has not been fully elucidated. In this study, we focused on the critical role of the pro-apoptosis Bcl-2 family members in I3M-induced apoptosis. We first observed I3M-induced apoptosis in a time- and dose-dependent manner in three different types of human cancer cells-cervical cancer HeLa, hepatoma HepG2 and colon cancer HCT116. Induction of the caspase cascade for both the extrinsic and intrinsic pathways was demonstrated, including caspase-8, -9 and -3 activation. Initiation of the death receptor pathway started with enhanced surface expression of DR4 and DR5, as well as increased total protein level, which correlated with the up-regulation of p53 and its transcriptional activity. Importantly, we found in HeLa cells that caspase-8 activation resulted in Bid cleavage, followed by Bax conformational change and hence the amplification of the apoptotic signals through the mitochondrial pathway. Consistently, stable knockdown of Bid abrogated I3M-induced Bax conformational change and cell death. Moreover, ectopic expression of a viral caspase inhibitor (CrmA) or Bcl-2 partially protected I3M-induced apoptosis. In conclusion, our results indicate that I3M mainly elicites apoptosis through extrinsic pathway with type II response mediated by the pro-apoptotic Bcl-2 family members (Bid and Bax). © 2008 Elsevier Inc. All rights reserved. | Source Title: | Biochemical Pharmacology | URI: | http://scholarbank.nus.edu.sg/handle/10635/108321 | ISSN: | 00062952 | DOI: | 10.1016/j.bcp.2008.01.021 |
Appears in Collections: | Staff Publications |
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