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

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

Research output: Contribution to journalArticle

26 Citations (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.

Original languageEnglish
Pages (from-to)1196-1205
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume79
Issue number4
DOIs
Publication statusPublished - 2011 Mar 15

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Keywords

  • Altered cross-linking
  • HSP27
  • Radiosensitization
  • Zerumbone

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

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