title: Dual role of insulin-like growth factor-1 in acetyl-CoA carboxylase-alpha activity in human colon cancer cells HCT-8: downregulating its expression and phosphorylation.
abstract: Insulin-like growth factor-1 (IGF-1) plays the role in cellular lipid synthesis and cell proliferation. However, the role of IGF-1 on the growth of colon cancer cell line HCT-8 is not clear. In this study, HCT-8 cells were exposed to IGF-1 at 0, 10, 50, or 100 ng/ml in serum-free medium. Fatty acid/lipid synthesis in HCT-8 cells was examined by 2-14C-acetate incorporation. HCT-8 cell growth and proliferation were determined by MTT assay and Trypan blue exclusive viable cell counting. We found that in serum starvation conditions, IGF-1 at 10-100 ng/ml induced dose-dependent down regulation of both the ACCα expression and the phosphorylation in HCT-8 cells, maintaining a balance in ACCα activity and lipid synthesis. IGF-1 reduced p-ATM, p-AMPK, and then p-ACCα protein levels in HCT-8 cells. IGF-1 increased p-Akt levels, but decreased p-ERK1/2 levels, leading to the decrease in ACCα protein and mRNA levels. Similarly, ERK1/2 inhibitor PD98059 reduced ACCα expression. IGF-1 influences neither HCT-8 cell growth nor their p53 protein levels and PARP cleavage. In a word, IGF-1 reduced ACCα phosphorylation via an ATM/AMPK signaling pathway and suppressed ACCα expression through an ERK1/2 transduction, playing a dual role in regulating ACCα activity and lipogenesis. This may render a cell with survival advantages under a serum starvation crisis, representing a novel mitogenic role of IGF-1.
authors.affiliation: School of Pharmaceutics, Central South University, Changsha, 410083, China.
authors.forename: Di-Xian
authors.initials: DX
authors.lastname: Luo
authors.forename: Xu-hong
authors.initials: XH
authors.lastname: Peng
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Liao
authors.forename: Deliang
authors.initials: D
authors.lastname: Cao
authors.forename: Longjiang
authors.initials: L
authors.lastname: Li
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis; D005419:Flavonoids / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000235:genetics*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D005419:Flavonoids; D025521:Tumor Suppressor Proteins; D007334:Insulin-Like Growth Factor I; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000103:Acetyl-CoA Carboxylase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one