Butyrate inhibits oral cancer cell proliferation and regulates expression of secretory phospholipase A2-X and COX-2

Although surgical resection is the first choice for oral cancer. the development of new anti-cancer drugs is of great interest. The effect of the histone deacetylation inhibitor, sodium butyrate (NaBu) on oral cancer cell (OCC) HSC-3 and HSC-4 proliferation in vitro was investigated. The synthesis of rate-limiting enzymes such as sPL4(2) (-II4, -V, -X) and COX-2 was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, as well as PGE(2) by ELISA. NaBu acted in a concentration-dependent manner. Over 3 mM, it inhibited OCC proliferation, due to increased p21 expression and cell cycle arrest in the G(2)/M-phase. At low concentration (<= 1 mM), NaBu showed no effects or enhanced cell proliferation. NaBu also regulated COX-2 and SPLA(2)-X expression. and augmented PGE(2) synthesis in OCC. These results indicate that NaBu is a novel candidate agent for the treatment of oral cancer. The treatment efficacy must be investigated in additional experiments considering NaBu concentration and tumor cell heterogeneity.