Growth inhibitory effects of aromatic fatty acids on ovarian tumor cell lines

Epithelial ovarian cancer is a major cause of cancer-related mortality in w omen, making the search for new treatment modalities essential. Sodium phen ylacetate (NaPa), a phenylalanine derivative, has been shown to induce cyto stasis and differentiation by inhibiting protein isoprenylation, Similar ef fects have been observed with phenylbutyrate, a phenylacetate congener, We examined in parallel the growth inhibitory activity against human ovarian c arcinoma cell lines of phenylacetate, phenylbutyric acid (PB), and certain related compounds, and comparisons were made with lovastatin, On a molar ba sis, hydroxykynurenine and kynurenine showed the highest activity followed by PB and NaPa, Ovarian carcinoma cell lines were also sensitive to lovasta tin in micromolar concentrations. Additive effects were observed when PB wa s combined with cisplatin or when NaPa or PB were combined with lovastatin, NaPa and PB, but not kynurenine, inhibited incorporation of [H-3]mevalonat e into ovarian carcinoma cells, An immune modulatory role might also be sug gested for PB because it resulted in increased ovarian tumor cell expressio n of human leukocyte antigen class I and the cluster of differentiation mol ecule CD58, whereas transforming growth factor-beta 2 expression was decrea sed. Phenylbutyrate, which is the ester form of PB, has shown acceptable ph armacological properties and clinical responses in patients with other mali gnancies, and might be considered for evaluation in ovarian cancer.