cerulenin and Mouth-Neoplasms

This study was undertaken to determine the characteristics of fatty acid synthesis in squamous carcinoma cells and to assess the possibility of exploiting this synthesis pathway in anticancer therapy. Incorporation of [(3)H]acetate into total lipids of the TCA-83 squamous carcinoma cell line and normal gingival fibroblasts was measured. The effects of cerulenin, a specific, potent, noncompetitive inhibitor of fatty acid synthase (FAS), on growth of TCA-83 cells and normal gingival fibroblasts was determined by the MTT method, and the effect of cerulenin on apoptosis was determined by electrophoresis of cellular DNA. Incorporation of [(3)H]acetate into total lipids was significantly higher in TCA-83 cells (68 +/- 12.7 cpm per 2 x 10(5) cells) than in normal gingival fibroblasts (13 +/- 4.2 cpm per 2 x 10(5) cells; P = 0.011). Cerulenin inhibited TCA-83 cell growth in a dose-dependent manner, even at 2.5 microg/ml, a concentration at which normal gingival fibroblasts were not inhibited. After exposure to cerulenin, TCA-83 cells showed typical apoptotic DNA ladders. These results indicate that cerulenin exerts selective cytotoxic effects on squamous carcinoma cells and can induce their apoptosis. These findings suggest that targeting of fatty acid synthesis may be useful in the treatment of squamous cell carcinomas.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cerulenin; Enzyme Inhibitors; Fatty Acid Synthases; Fatty Acids; Humans; Mouth Neoplasms; Pilot Projects

Inhibition of cerulenin on the endogenous fatty acid synthetic activities of oral squamous cell carcinoma (OSCC) and normal oral mucosa was assayed.. Squamous cell carcinoma and normal oral mucosa were collected fresh from surgical specimens. The collected tissues were minced in RPMI 1640 and divided into 3 groups: cerulenin treated, dimethylsulfoxide treated, and control. The tissues were incubated in [1(2)-(14)C]acetic acid, sodium salt for the last 2.5 hours of the treatment at 37 degrees C in 5% CO(2). After labeling, total lipids were extracted and counted for (14)C by scintillation counting.. Endogenous fatty acid synthetic activities of oral squamous cell caranoma in the cerulenin-treated group decreased by 19% at 1 hour, 64% at 2 hours, and 87% at 4 hours; remained nearly unchanged in the dimethylsulfoxide-treated group; and increased slightly in the control group. The oral mucosa tissues were only mildly affected by cerulenin in fatty acid synthesis.. Cerulenin significantly inhibits fatty acid synthetic activity in squamous cell carcinoma and only mildly affected the oral mucosa, indicating that the fatty acid synthetic pathway may be exploited as a target for developing anticancer drugs.

Topics: Aged; Analysis of Variance; Carbon Radioisotopes; Carcinoma, Squamous Cell; Cerulenin; Culture Techniques; Dimethyl Sulfoxide; Enzyme Inhibitors; Fatty Acid Synthases; Fatty Acids; Female; Humans; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Radiopharmaceuticals; Solvents; Time Factors