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Overcoming HSP27-mediated resistance by altered dimerization of HSP27 using small molecules

Title
Overcoming HSP27-mediated resistance by altered dimerization of HSP27 using small molecules
Authors
Kim, Jee HyeJung, Ye JinChoi, ByeolLee, Na LimLee, Hae JunKwak, Soo YeonKwon, YoungjooNa, YounghwaLee, Yun-Sil
Ewha Authors
권영주이윤실
SCOPUS Author ID
권영주scopus; 이윤실scopus
Issue Date
2016
Journal Title
ONCOTARGET
ISSN
1949-2553JCR Link
Citation
vol. 7, no. 33, pp. 53178 - 53190
Keywords
HSP27 inhibitionaltered dimerizationovercoming resistancecombination therapy
Publisher
IMPACT JOURNALS LLC
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Heat shock protein 27 (HSP27, HSPB1) is an anti-apoptotic protein characterized for its tumorigenic and metastatic properties, and now referenced as a major therapeutic target in many types of cancer. The biochemical properties of HSP27 rely on a structural oligomeric and dynamic organization that is important for its chaperone activity. Down-regulation by small interfering RNA or inhibition with a dominant-negative mutant efficiently counteracts the anti-apoptotic and protective properties of HSP27. However, unlike other HSPs such as HSP90 and HSP70, small molecule approaches for neutralization of HSP27 are not well established because of the absence of an ATP binding domain. Previously, we found that a small molecule, zerumbone (ZER), induced altered dimerization of HSP27 by cross linking the cysteine residues required to build a large oligomer, led to sensitization in combination with radiation. In this study, we identified another small molecule, a xanthone compound, more capable of altering dimeric HSP27 than ZER and yielding sensitization in human lung cancer cells when combined with HSP90 inhibitors or standard anticancer modalities such as irradiation and cytotoxic anticancer drugs. Therefore, altered dimerization of HSP27 represents a good strategy for anticancer therapy in HSP27-overexpressing cancer cells.
DOI
10.18632/oncotarget.10629
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약학대학 > 약학과 > Journal papers
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