Effects of sodium butyrate on growth, differentiation, and apoptosis in head and neck squamous carcinoma cell lines

Background. Biologic agents that reverse early changes in the aerodigestive tract mucosa have potential treatment applications for patients with field cancerization of the upper aerodigestive tract. Sodium butyrate (BA) is a normal dietary constituent that induces differentiation and inhibits growth in several malignant cell types in vitro, but its effect on head and neck squamous cell carcinoma (HNSCC) has not been evaluated. Methods. Using five HNSCC cell lines, the effects of BA on cell proliferation and apoptosis were examined by colorimetric and fluorescence-labeling methods, and the expression of differentiation markers and apoptosis-related proteins were analyzed using Western and Northern blotting, flow cytometry, and cell cycle analysis. Results. BA-induced growth inhibition and apoptosis in HNSCC cells at millimolar concentrations. Apoptosis induction did not depend on the p53 status of the cell lines or on expression of members of the Bcl-2/Bax family. Conclusions. These results demonstrate that butyrate has activity against HNSCC in vitro and may have clinical applications for management of HNSCC patients. (C) 2000 John Wiley and Sons, Inc.