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Altered Cross-Linking of HSP27 by Zerumbone as a Novel Strategy for Overcoming HSP27-Mediated Radioresistance.
MedLine Citation:
PMID:  21353161     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
PURPOSE: HSP27 or HSP25 negatively regulates apoptosis pathways after radiation or chemotherapeutic agents. Abrogation of HSP27 function may be a candidate target for overcoming radio- and chemoresistance.
METHODS AND MATERIALS: Zerumbone (ZER), a cytotoxic component isolated from Zingiber zerumbet smith. Clonogenic survival assay and flow cytometry after Annexin V staining were performed to determine in vitro sensitization effects of ZER with ionizing radiation. A nude mouse xenografting system was also applied to detect in vivo radiosensitizing effects of ZER.
RESULTS: ZER produced cross-linking of HSP27, which was dependent on inhibition of the monomeric form of HSP27. ZER was directly inserted between the disulfide bond in the HSP27 dimer and modified normal HSP27 dimerization. Pretreatment with ZER before radiation inhibited the binding affinity between HSP27 and apoptotic molecules, such as cytochrome c and PKCδ, and induced sensitization in vitro and in an in vivo xenografted nude mouse system. Structural analogs lacking only the carbonyl group in ZER, such as α-humulene (HUM) and 8-hydroxy-humulen (8-OH-HUM), did not affect normal cross-linking of HSP27 and did not induce radiosensitization.
CONCLUSIONS: We suggest that altered cross-linking of HSP27 by ZER is a good strategy for abolishing HSP27-mediated resistance.
Authors:
Seo-Hyun Choi; Yoon-Jin Lee; Woo Duck Seo; Hae-June Lee; Joo-Won Nam; Yoo Jin Lee; Joon Kim; Eun-Kyoung Seo; Yun-Sil Lee
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  79     ISSN:  1879-355X     ISO Abbreviation:  Int. J. Radiat. Oncol. Biol. Phys.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1196-205     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Division of Radiation Effects, Korea Institute of Radiological and Medical Science, Seoul, Korea; School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
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