Fatty acid synthase inhibitors cerulenin and C75 retard growth and induce caspase-dependent apoptosis in human melanoma A-375 cells.

摘要: Fatty acid synthase (FAS) has been shown previously to be highly expressed in breast and prostate carcinomas, but low expression level normal tissues. We also found this study that FAS was a number of cancer cell lines different histotypes. The growth-inhibitory effects inhibitors cerulenin C75 were then investigated on these lines, particularly the human melanoma A-375. MTT assay revealed proliferation viability reduced dose- time-dependently by 20.8%-87.1% control levels after 24 48 h treatment with 20-160 microM inhibitor. Immunoblotting studies showed both induced poly(ADP-ribose) polymerase (PARP) cleavage cells dose-dependently. Procaspase-3 processed into active smaller 17 19 kDa subunits, administration pan-caspase inhibitor Z-VAD-FMK completely rescued from PARP cleavage. This indicated cerulenin- C75-induced apoptosis involved caspase activation. proapoptotic further confirmed using confocal microscopy annexin-V FITC propidium iodide staining. DNA flow cytometric demonstrated accumulated G2/M preceding elevation sub G1 or apoptotic fragmented DNA. cycle arrest associated p21 depletion Bcl-xL Mcl-1, respectively. Results suggest retard growth A-375 cells, involving activation caspase-dependent apoptosis.