title: Fatty acid synthase inhibition induces differential expression of genes involved in apoptosis and cell proliferation in ocular cancer cells.
abstract: Fatty acid synthase (FASN), a lipogenic multienzyme complex, is overexpressed in the ocular cancer, retinoblastoma, and is strongly correlated with tumor invasion. Dietary nutrients are reported to exert anticancer effects through inhibition of lipid metabolism. Differential gene expression in cultured retinoblastoma cells induced by cerulenin, a chemical inhibitor of FASN, was evaluated by cDNA microarray analysis. Cerulenin treatment resulted in significant upregulation of cytochrome c (CYCS) by 1.2-fold, whereas S-phase kinase-associated protein-2 (SKP2), a negative regulator of cell cycle, and the lipid metabolic genes (PPARA, RXRA, and ACACB) were significantly downregulated by -1.59-, -1.8-, -1.83-, and -1.5-fold, respectively, in comparison with untreated cancer cells. The expressions of key differentially expressed genes were confirmed by quantitative real-time PCR. The altered expression of genes involved in cell proliferation, cell signaling, apoptosis, and cell cycle, correlated with the anticancer effects of cerulenin. FASN inhibition may thus be a potential strategy in retinoblastoma management.
authors: Department of Biological Sciences, Birla Institute of Technology & Science (BITS), Pilani, Rajasthan, India. deepa@pilani.bits-pilani.ac.in
authors: Perinkulam Ravi
authors: PR
authors: Deepa
authors: Suryanarayanan
authors: S
authors: Vandhana
authors: Subramanian
authors: S
authors: Krishnakumar
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002569:Cerulenin / Q000494:pharmacology*; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054872:Fatty Acid Synthesis Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D047493:PPAR alpha / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D019572:Retinal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D012175:Retinoblastoma / Q000188:drug therapy* / Q000235:genetics; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D054872:Fatty Acid Synthesis Inhibitors; D047493:PPAR alpha; D047495:PPAR gamma; D044786:S-Phase Kinase-Associated Proteins; D002569:Cerulenin; D045304:Cytochromes c; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; C520105:ACACB protein, human; D000103:Acetyl-CoA Carboxylase