hydrazinocurcumin and Mouth-Neoplasms

Altered histone acetylation is associated with several diseases, including cancer. We report here that, unlike in most cancers, histones are found to be highly hyperacetylated in oral squamous cell carcinoma (OSCC; oral cancer) patient samples. Mechanistically, overexpression, as well as enhanced autoacetylation, of p300 induced by nucleophosmin (NPM1) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) causes the hyperacetylation, which is nitric oxide (NO) signal dependent. Inhibition of the histone acetyltransferase (HAT) activity of p300 by a water-soluble, small molecule inhibitor, Hydrazinocurcumin (CTK7A), substantially reduced the xenografted oral tumor growth in mice. These results, therefore, not only establish an epigenetic target for oral cancer, but also implicate a HAT inhibitor (HATi) as a potential therapeutic molecule.

Topics: Acetylation; Animals; Cell Proliferation; Cellular Senescence; Curcumin; Enzyme Inhibitors; Gene Expression Regulation, Neoplastic; Glyceraldehyde-3-Phosphate Dehydrogenases; HeLa Cells; Histone Acetyltransferases; Histones; Humans; Hydrazines; Mice; Mice, Nude; Mouth Neoplasms; Nitric Oxide; Nuclear Proteins; Nucleophosmin; p300-CBP Transcription Factors; Solubility; Up-Regulation; Water