A pilot study of fatty acid metabolism in oral squamous cell carcinoma.
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.
Zhang
Y
Y
Department of Oral and Maxillofacial Surgery, Peking University School of Stomatology, Beijing 100081, PR China. zhangyie1101@sohu.com
Guo
C
C
Yu
G
G
D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002569:Cerulenin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism*; D010865:Pilot Projects
D004791:Enzyme Inhibitors; D005227:Fatty Acids; D002569:Cerulenin; D064429:Fatty Acid Synthases