Potent in vivo anti-breast cancer activity of IN-2001, a novel inhibitor of histone deacetylase, in MMTV/c-Neu Mice

Ki E. Joung, Kyung N. Min, Jin Y. An, Dae Kee Kim, Gu Kong, Y. Yhong Sheen

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

A novel synthetic inhibitor of histone deacetylase (HDAC), 3-(4-dimethylaminophenyl)-N-hydroxy-2-propenamide (IN-2001), was examined for its antitumor activity and for the underlying molecular mechanisms of any such activity. IN-2001 effectively inhibited cellular HDAC activity (IC50, 5.42 nmol/L) in MCF-7 human breast cancer cells. Based on the Western blot analysis, this HDAC inhibitory effect of IN-2001 was confirmed by an increase in histone H4 acetylation from the IN-2001-treated breast cancer cells. IN-2001 suppressed mammary tumor growth in MMTV/c-Neu transgenic mice and also showed higher apoptotic index and lower lymphatic invasion compared with controls. In human breast cancer cells (MCF-7, T47D, MDA-MB-231, and MDA-MB-468), IN-2001 induced cell cycle arrest at G2-M phase through up-regulation of p21WAF1 and p27KIP1 and eventually caused apoptosis. IN-2001-induced apoptosis was caspase dependent and seems mediated through an increase in Bax/Bcl-2 ratio. Taken together, our data indicate that this novel HDAC inhibitor is a promising therapeutic agent against human breast cancer.

Original languageEnglish
Pages (from-to)5394-5402
Number of pages9
JournalCancer Research
Volume66
Issue number10
DOIs
StatePublished - 15 May 2006

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