| Description: |
TOFA (5-tetradecyloxy-2-furoic acid) is cytotoxic to lung cancer cells NCI-H460 and colon carcinoma cells HCT-8 and HCT-15, with an IC50 at approximately 5.0, 5.0, and 4.5 μg/mL, respectively. TOFA at 1.0–20.0 μg/mL effectively blocks fatty acid synthesis and induces cell death in a dose-dependent manner. TOFA is found to be cytotoxic to COC1 and COC1/DDP cells with IC50 values of ~26.1 and 11.6 µg/mL, respectively. TOFA inhibits the proliferation of the cancer cells examined in a time and dose dependent manner, arrests the cells in the G0/G1 cell cycle phase and induces apoptosis. Acetyl-CoA-carboxylase-α (ACCA) is a key enzyme in the regulation of fatty acids synthesis. Inhibition of ACCA by TOFA decreases fatty acid synthesis and induces caspase activation and cell death in most PCa cell lines.TOFA inhibits COC1/DDP cell growth in ovarian tumor mouse xenografts. The tumor growth rate is signifi¬cantly inhibited by TOFA compared with the DMSO treated control mice (1649±356.3 vs. 5128±390.4 mm3. No toxicity is observed in the heart, liver, spleen, lung, kidney and intestinal tissues. By inhibiting ACC, TOFA may be a promising small molecule agent for ovarian cancer therapy. |
