Targeting Mutant p53 by a SIRT1 Activator YK-3-237 Inhibits the Proliferation of Triple-Negative Breast Cancer Cells

摘要: // Yong Weon Yi 1,* , Hyo Jin Kang Hee Jeong Kim 1 Yali Kong 3 Milton L. Brown and Insoo Bae 1,2,3 Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 2 Radiation Medicine, Center for Drug Discovery, * These authors contributed equally Correspondence: Brown, email: Bae, Keywords : mutant p53 (mtp53), deacetylation, SIRT1, activator, triple-negative breast cancer (TNBC) Received May 31, 2013 Accepted June 20, Published July 5, Abstract Many types mutations in tumor suppressor are oncogenic through gain-of-function. Therefore, targeting (mtp53) is a promising therapeutic approach to fight against many cancers. We report here small molecule compound YK-3-237 that reduces acetylation mtp53 exhibits anti-proliferative effects toward cells carrying mtp53. activates SIRT1 enzyme activities vitro deacetylation both wild type (WTp53) SIRT1-dependent manner. Deacetylation resulted depletion protein level up-regulated the expression WTp53-target genes, PUMA NOXA. also induces PARP-dependent apoptotic cell death arrests cycle at G2/M phase TNBC cells. Taken together, our data suggest potential target treat human