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Altered cross-linking of HSP27 by Zerumbone as a novel strategy for overcoming HSP27-mediated radioresistance

Title
Altered cross-linking of HSP27 by Zerumbone as a novel strategy for overcoming HSP27-mediated radioresistance
Authors
Choi S.-H.Lee Y.-J.Seo W.D.Lee H.-J.Nam J.-W.Lee Y.J.Kim J.Seo E.-K.Lee Y.-S.
Ewha Authors
서은경이윤실
SCOPUS Author ID
서은경scopus; 이윤실scopus
Issue Date
2011
Journal Title
International Journal of Radiation Oncology Biology Physics
ISSN
0360-3016JCR Link
Citation
vol. 79, no. 4, pp. 1196 - 1205
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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. Copyright © 2011 Elsevier Inc.
DOI
10.1016/j.ijrobp.2010.10.025
Appears in Collections:
약학대학 > 약학과 > Journal papers
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