| First Author | Joung KE | Year | 2006 |
| Journal | Cancer Res | Volume | 66 |
| Issue | 10 | Pages | 5394-402 |
| PubMed ID | 16707467 | Mgi Jnum | J:109053 |
| Mgi Id | MGI:3625650 | Doi | 10.1158/0008-5472.CAN-05-3835 |
| Citation | Joung KE, et al. (2006) Potent in vivo anti-breast cancer activity of IN-2001, a novel inhibitor of histone deacetylase, in MMTV/c-Neu mice. Cancer Res 66(10):5394-402 |
| abstractText | 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 (IC(50), 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 G(2)-M phase through up-regulation of p21(WAF1) and p27(KIP1) 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. |
