| Curcumin induces Apaf-1 dependent, p21-mediated caspase activation and apoptosis. | |
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MedLine Citation:
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PMID: 22101335 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Previous studies have demonstrated that curcumin induces mitochondria-mediated apoptosis. However, understanding of the molecular mechanisms underlying curcumin-induced cell death remains limited. In this study, we demonstrate that curcumin treatment of cancer cells caused dose- and time-dependent caspase-3 activation, which is required for apoptosis as confirmed using the pan caspase inhibitor, z-VAD. Knockdown experiments and knockout cells excluded a role of caspase-8 in curcumin-induced caspase-3 activation. In contrast, Apaf-1 deficiency or silencing inhibited the activity of caspase-3, pointing to a requisite role of Apaf-1 in curcumin-induced apoptotic cell death. Curcumin treatment led to Apaf-1 upregulation both at the protein and mRNA levels. Cytochrome c release from mitochondria to the cytosol in curcumin-treated cells was associated with upregulation of proapoptotic proteins such as Bax, Bak, Bid, and Bim. Crosslinking experiments demonstrated Bax oligomerization during curcumin-induced apoptosis, suggesting that induced expression of Bax, Bid, and Bim causes Bax-channel formation on the mitochondrial membrane. The release of cytochrome c was unaltered in p53-deficient cells, whereas absence of p21 blocked cytochrome c release, caspase activation, and apoptosis. Importantly, p21-deficiency resulted in reduced expression of Apaf-1 during curcumin treatment, indicating a requirement of p21 in Apaf-1 dependent caspase activation and apoptosis. Together, our findings demonstrate that Apaf-1, Bax, and p21 as novel potential targets for curcumin or curcumin-based anticancer agents. |
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Authors:
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Raghu Gogada; Michael Amadori; Honghao Zhang; Anthony Jones; Alissa Verone; Jason Pitarresi; Sirisha Jandhyam; Varun Prabhu; Jennifer D Black; Dhyan Chandra |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-01 |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 10 ISSN: 1551-4005 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-11-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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The Department of Pharmacology and Therapeutics; Roswell Park Cancer Institute; Buffalo, NY USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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