Withaferin A Induces Proteasome-Dependent Degradation of Breast Cancer Susceptibility Gene 1 and Heat Shock Factor 1 Proteins in Breast Cancer Cells
Issue Date
2012-06-01Author
Zhang, Xuan
Timmermann, Barbara N.
Samadi, Abbas K.
Cohen, Mark S.
Publisher
Hindawi Publishing Corporation
Type
Article
Article Version
Scholarly/refereed, publisher version
Metadata
Show full item recordAbstract
The purpose of this study was to examine the regulation of prosurvival factors heat shock factor 1 (HSF1) and breast cancer susceptibility gene 1 (BRCA1) by a natural withanolide withaferin A (WA) in triple negative breast cancer cell lines MDA-MB-231 and BT20. Western analysis was used to examine alternations in HSF1 and BRCA1 protein levels following WA treatment. A protein synthesis inhibitor cycloheximide and a proteasome inhibitor MG132 were used to investigate the mechanisms of HSF1 and BRCA1 regulation by WA. It was found that WA induced a dose-dependent decrease in HSF1 and BRCA1 protein levels. Further analysis showed that levels of HSF1 and BRCA1 proteins decreased rapidly after WA treatment, and this was attributed to WA-induced denaturation of HSF1 and BRCA1 proteins and subsequent degradation via proteasome-dependent, and protein-synthesis dependent mechanism. In summary, WA induces denaturation and proteasomal degradation of HSF1 and BRCA1 proteins. Further studies are warranted to examine the contribution of HSF1 and BRCA1 depletion to the anticancer effects of WA in breast cancer.
Description
This is the publisher's version, also available electronically from "http://www.hindawi.com".
Collections
- Pharmacy Scholarly Works [293]
Citation
Zhang, X., Timmmerman, B. N., Samadi, A. & Cohen, M. (2012) Withaferin A Induces Proteasome-Dependent Degradation of Breast Cancer Susceptibility Gene 1 and Heat Shock Factor 1 Proteins in Breast Cancer Cells. ISRN Biochemistry, 2012, 6pg. http://www.dx.doi.org/10.5402/2012/707586
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