Objectives/hypothesis: Head and neck squamous cell carcinoma (HNSCC) is a major cause of mortality. Despite advances in therapeutic modalities, recurrences and second primaries are commonly observed. Biological agents that can suppress growth of tumors that are otherwise difficult to treat are greatly needed. The present study examined the effects of short-chain fatty acids on HNSCC cell lines.
Study design: The effects of short-chain fatty acids on HNSCC cells was examined using tissue culture and immunoblotting techniques.
Methods: The effects of four short-chain fatty acids, arginine butyrate, alpha-methyl hydrocinnamic acid, 2,2-dimethylbutyrate, and alpha-lipoic acid, were evaluated on four HNSCC cell lines (FaDu, SCC9, SCC25, and Detroit-562). Proliferation assays were performed by means of spectrophotometric techniques. Histone deacetylase activity was assessed by identifying the amount of acetylated histone H4. Involucrin expression was determined to assess cellular differentiation.
Results: Inhibition of cellular proliferation was determined after 5 days of incubation with increasing doses with short-chain fatty acids. Arginine butyrate and alpha-lipoic acid were most effective in suppressing growth. Arginine butyrate demonstrated strong histone deacetylase inhibition in FaDu cells, while not inducing cellular differentiation. The short-chain fatty acid alpha-lipoic acid demonstrated weak histone deacetylase inhibition but was the only short-chain fatty acid that induced involucrin expression in at least two of the cell lines. Histone deacetylase inhibitory activity or induction of involucrin expression correlated with suppression of cell growth.
Conclusions: Short-chain fatty acids have variable effects on HNSCC cells. Arginine butyrate and alpha-lipoic acid are the most effective in suppressing growth and appear to do so through different biochemical mechanisms. These compounds warrant further research as chemotherapeutic or chemopreventive agents in HNSCC.