| SNX-2112, an Hsp90 inhibitor, induces apoptosis and autophagy via degradation of Hsp90 client proteins in human melanoma A-375 cells. | |
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MedLine Citation:
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PMID: 22182451 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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SNX-2112 is an Hsp90 inhibitor which is currently undergoing multiple Phase 1 clinical trials; however, its mechanism of action needs to be further elaborated. Here we investigated the effects of SNX-2112 in A-375 cells. SNX-2112 induced the degradation of multiple Hsp90 client proteins, activated both the mitochondrial-mediated and death receptor-mediated apoptotic pathways, downregulated Bcl-2 and Bcl-xL, upregulated Bid, cleaved caspase-9, caspase-7, caspase-3 and PARP, and activated caspase-8. The general caspase inhibitor, z-VAD-fmk, did not completely abolish SNX-2112-induced cell death. SNX-2112 induced autophagy in a time- and dose-dependent manner via Akt/mTOR/p70s6k inhibition. SNX-2112 induces significant apoptosis and autophagy in human melanoma A-375 cells, and may be an effective targeted therapy agent. |
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Authors:
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Kai-Sheng Liu; Hui Liu; Shao-Xiang Wang; Jin-Huan Qi; Qiu-Yun Liu; Zhong Liu; Min Xia; Guo-Wen Xing; Yi-Fei Wang |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-16 |
Journal Detail:
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Title: Cancer letters Volume: - ISSN: 1872-7980 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Ireland Ltd. |
Affiliation:
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Guangzhoujinan Biomedicine Research and Development Center;Guangdong Provincial Key Laboratory of Bioengineering Medicine;National Engineering Research Center of Genetic Medicine, Jinan University, No.601, West Huangpu Road, Guangzhou 510632, China; Pharmacy College, Jinan University, Guangzhou 510632, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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