Fisetin, a dietary flavonoid, induces apoptosis of cancer cells by inhibiting HSF1 activity through blocking its binding to the hsp70 promoter = HSF1 전사조절인자가 프로모터에 결합하는 단계를 저해하여 활성을 저해함으로써 암세포 사멸을 유도하는 Fisetin

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Title
Fisetin, a dietary flavonoid, induces apoptosis of cancer cells by inhibiting HSF1 activity through blocking its binding to the hsp70 promoter = HSF1 전사조절인자가 프로모터에 결합하는 단계를 저해하여 활성을 저해함으로써 암세포 사멸을 유도하는 Fisetin
Author(s)
Joo Ae Kim; Somyoung Lee; Da-Eun Kim; Moonil Kim; Byoung-Mog Kwon; Dong Cho Han
Bibliographic Citation
Carcinogenesis, vol. 36, no. 6, pp. 696-706
Publication Year
2015
Abstract
Heat shock factor 1 (HSF1) is a transcription factor for heat shock proteins (HSPs) expression that enhances the survival of cancer cells exposed to various stresses. HSF1 knockout suppresses carcinogen-induced cancer induction in mice. Therefore, HSF1 is a promising therapeutic and chemopreventive target. We performed cell-based screening with a natural compound collection and identified fisetin, a dietary flavonoid, as a HSF1 inhibitor. Fisetin abolished heat shock-induced luciferase activity with an IC50 of 14 μM in HCT-116 cancer cells. The treatment of HCT-116 with fisetin inhibited proliferation with a GI50 of 23 μM. When the cells were exposed to heat shock in the presence of fisetin, the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 (Bcl-2-associated athanogene domain 3), were inhibited. HSP70/BAG3 complexes protect cancer cells from apoptosis by stabilizing anti-apoptotic Bcl-2 family proteins. The downregulation of HSP70/BAG3 by fisetin significantly reduced the amounts of Bcl-2, Bcl-xL and Mcl-1 proteins, subsequently inducing apoptotic cell death. Chromatin immunoprecipitation assays showed that fisetin inhibited HSF1 activity by blocking the binding of HSF1 to the hsp70 promoter. Intraperitoneal treatment of nude mice with fisetin at 30 mg/kg resulted in a 35.7% (P < 0.001) inhibition of tumor growth.
ISSN
0143-3334
Publisher
Oxford Univ Press
DOI
http://dx.doi.org/10.1093/carcin/bgv045
Type
Article
Appears in Collections:
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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