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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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

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.[1]

References

  1. Potent in vivo anti-breast cancer activity of IN-2001, a novel inhibitor of histone deacetylase, in MMTV/c-Neu mice. Joung, K.E., Min, K.N., An, J.Y., Kim, D.K., Kong, G., Sheen, Y.Y. Cancer Res. (2006) [Pubmed]
 
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