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

23 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

Fingerprint

mice
cytometry
cytochromes
apoptosis
disulfides
staining
radiation
dimerization
ionizing radiation
pretreatment
affinity
drugs
dimers
Nude Mice
analogs
Radiation
Radiation-Sensitizing Agents
Heterologous Transplantation
zerumbone
molecules

Keywords

  • Altered cross-linking
  • HSP27
  • Radiosensitization
  • Zerumbone

ASJC Scopus subject areas

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

Cite this

Altered cross-linking of HSP27 by Zerumbone as a novel strategy for overcoming HSP27-mediated radioresistance. / Choi, Seo Hyun; Lee, Yoon Jin; Seo, Woo Duck; Lee, Hae June; Nam, Joo Won; Lee, Yoo Jin; Kim, Joon; Seo, Eun Kyoung; Lee, Yun Sil.

In: International Journal of Radiation Oncology Biology Physics, Vol. 79, No. 4, 15.03.2011, p. 1196-1205.

Research output: Contribution to journalArticle

Choi, Seo Hyun ; Lee, Yoon Jin ; Seo, Woo Duck ; Lee, Hae June ; Nam, Joo Won ; Lee, Yoo Jin ; Kim, Joon ; Seo, Eun Kyoung ; Lee, Yun Sil. / Altered cross-linking of HSP27 by Zerumbone as a novel strategy for overcoming HSP27-mediated radioresistance. In: International Journal of Radiation Oncology Biology Physics. 2011 ; Vol. 79, No. 4. pp. 1196-1205.
@article{a0c25c6ce54545fb9b9e21ac97e02e13,
title = "Altered cross-linking of HSP27 by Zerumbone as a novel strategy for overcoming HSP27-mediated radioresistance",
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.",
keywords = "Altered cross-linking, HSP27, Radiosensitization, Zerumbone",
author = "Choi, {Seo Hyun} and Lee, {Yoon Jin} and Seo, {Woo Duck} and Lee, {Hae June} and Nam, {Joo Won} and Lee, {Yoo Jin} and Joon Kim and Seo, {Eun Kyoung} and Lee, {Yun Sil}",
year = "2011",
month = "3",
day = "15",
doi = "10.1016/j.ijrobp.2010.10.025",
language = "English",
volume = "79",
pages = "1196--1205",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Altered cross-linking of HSP27 by Zerumbone as a novel strategy for overcoming HSP27-mediated radioresistance

AU - Choi, Seo Hyun

AU - Lee, Yoon Jin

AU - Seo, Woo Duck

AU - Lee, Hae June

AU - Nam, Joo Won

AU - Lee, Yoo Jin

AU - Kim, Joon

AU - Seo, Eun Kyoung

AU - Lee, Yun Sil

PY - 2011/3/15

Y1 - 2011/3/15

N2 - 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.

AB - 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.

KW - Altered cross-linking

KW - HSP27

KW - Radiosensitization

KW - Zerumbone

UR - http://www.scopus.com/inward/record.url?scp=79951876376&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951876376&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2010.10.025

DO - 10.1016/j.ijrobp.2010.10.025

M3 - Article

VL - 79

SP - 1196

EP - 1205

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 4

ER -