Phenylacetate enhances the antiproliferative effect of retinoic acid in follicular thyroid cancer.

ABSTRACT

BACKGROUND: Retinoic acid (RA) has antiproliferative as well as redifferentiating effects in thyroid cancers. Similar effects have been seen with phenylacetate (PA) therapy. These observations prompted us to evaluate the potential antiproliferative effects of the combination of RA and PA in follicular thyroid cancer. METHODS: Three follicular cell lines were treated in vitro with varying concentrations of all-trans RA or PA alone or in combination. Growth was measured by dimethyl-thiazol-diphenyltetrazolium bromide assays. RESULTS: RA (1-2.5 micromol/L) and PA (1-10 mmol/L) alone inhibited cell growth in a time- and dose-dependent manner, with maximum effect at 5 days. The combination of RA and PA had synergistic antiproliferative effects. In the FTC-133 cell line, RA alone (2.5 micromol/L) inhibited growth 16% and PA alone (10 mmol/L) inhibited growth 35% versus controls, whereas the combination of the 2 inhibited growth by 60% at 5 days (P < .005). Similar results were seen with FTC-236 and FTC-238 cell lines. CONCLUSIONS: Our results support that RA and PA have antiproliferative effects in follicular thyroid cancer and are synergistic. The combination of RA and PA may be beneficial in the treatment of advanced thyroid cancers for which conventional therapy fails or as an adjuvant to radioactive iodine therapy in aggressive tumors.