A characteristic feature of
cancer cells is the activation of de novo
fatty acid synthesis. Acetyl‑CoA carboxylase (ACC) is a key
enzyme in
fatty acid synthesis, accelerating the reaction that carboxylates cytosolic acetyl‑CoA to form malonyl‑CoA. ACC is highly expressed in several types of human
cancer and is important in breast and
prostate cancer cell growth. The aim of the present study was to investigate the effects of 5‑tetradecyloxy‑2‑furoic
acid (
TOFA), an allosteric inhibitor of ACC, on the proliferation and cell cycle progression of the
ovarian cancer cell lines COC1 and COC1/DDP.
TOFA was found to be cytotoxic to COC1 and COC1/DDP cells with a 50% inhibitory concentration (IC50) of ~26.1 and 11.6 µg/ml, respectively.
TOFA inhibited the proliferation of the
cancer cells examined in a time‑ and dose‑dependent manner, arrested the cells in the G0/G1 cell cycle phase and induced apoptosis. The expression of the cell cycle regulating
proteins cyclin D1 and
cyclin-dependent kinase (CDK) 4, as well as the expression of the apoptosis‑related
proteins caspase‑3 and Bcl‑2, were detected by western blot analysis.
Cyclin D1, CDK4 and Bcl‑2
protein expression was inhibited by
TOFA, while caspase‑3 was cleaved and activated. To the best of our knowledge, the present study demonstrated for the first time that
TOFA inhibits COC1/DDP cell growth in ovarian
tumor mouse xenografts. By inhibiting ACC,
TOFA may be a promising small molecule agent for
ovarian cancer therapy.