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The effects of heat shock protein 90 inhibitors on apoptosis and viral replication in primary effusion lymphoma cells.
MedLine Citation:
PMID:  22687408     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by Kaposi's sarcoma-associated herpesvirus (KSHV) in immunosuppressed patients and human immunodeficiency virus (HIV)-infected homosexual males. We evaluated the cytotoxic effects of heat shock protein 90 (HSP90) inhibitors on PEL cells. The HSP90 inhibitors geldanamycin (GA), 17(allylamino)-17-demethoxygeldanamycin (17-AAG), and radicicol dramatically inhibited cell proliferation and induced apoptosis of PEL cells through caspase activation. Furthermore, GA induced the stabilization of inhibitor of κB (IκB)α and reduced the phosphorylation of IκBα in PEL cells. HSP90 inhibitors suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB) in PEL cells. It is known that the constitutive activation of NF-κB signaling is essential for the survival of PEL cells and HSP90 contributes to promote activation of NF-κB signaling. The suppression of NF-κB signaling by HSP90 inhibitors may contribute to the induction of apoptosis in PEL cells. In addition, HSP90 activity is required for KSHV replication in KSHV latently infected PEL cells. GA, 17-AAG and radicicol reduced the production of progeny virus from PEL cells at low concentrations, which do not affect PEL cell growth. Our results suggest that HSP90 activity is required for both the survival of PEL cells and viral replication in PEL cells, and that pharmacologic inhibition of HSP90 may be an effective treatment for PEL and KSHV-related diseases.
Authors:
Chizuka Higashi; Chiaki Saji; Koji Yamada; Hiroki Kagawa; Rie Ohga; Takahiro Taira; Masahiro Fujimuro
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  35     ISSN:  1347-5215     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  725-30     Citation Subset:  IM    
Affiliation:
Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi.
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