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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

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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.

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Abbreviations

ACCα:

Acetyl-CoA carboxylase-α

AMPK:

AMP-activated protein kinase

ATM:

Ataxia telangiectasia mutated

ERK1/2:

Extracellular signal-regulated kinase 1/2

IGF-1:

Insulin-like growth factor-1

PI3K:

Phosphoinositide-3-kinase

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Authors and Affiliations

  1. School of Pharmaceutics, Central South University, Changsha, 410083, China

    Di-Xian Luo & Yan Xiong

  2. Department of Microbiology, Immunology and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, 913 N, Rutledge Street, Springfield, IL, 62702, USA

    Di-Xian Luo & Deliang Cao

  3. Institute of Pharmacy and Pharmacology, College of Pharmaceutics and Life Science, University of South China, Hengyang, 421001, China

    Di-Xian Luo & Duan-Fang Liao

  4. Department of Ultrasound Diagnosis, First People’s Hospital of Chenzhou City, Chenzhou, 423000, China

    Xu-hong Peng

  5. Department of Pharmacology, Guangzhou Medical University, Guangzhou, 510182, China

    Yan Xiong

  6. Department of Traditional Chinese Diagnostics, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 420108, China

    Duan-Fang Liao

  7. Department of Urology Surgery, Baoan District People’s Hospital, 168 Longjing-2 Road, Baoan, Shenzhen, 518101, China

    Longjiang Li

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  1. Di-Xian Luo
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  2. Xu-hong Peng
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  4. Duan-Fang Liao
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Correspondence to Longjiang Li.

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Di-Xian Luo and Xu-hong Peng contributed equally to this work.

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Luo, DX., Peng, Xh., Xiong, Y. et al. 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. Mol Cell Biochem 357, 255–262 (2011). https://doi.org/10.1007/s11010-011-0896-0

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