Food Science and Biotechnology

Korean Society of Food Science and Technology (한국식품과학회)
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Resveratrol Downregulates Acetyl-CoA Carboxylase $\alpha$ and Fatty Acid Synthase by AMPK-mediated Downregulation of mTOR in Breast Cancer Cells

  • Park, Sahng-Wook (Department of Biochemistry and Molecular Biology, Yonsei University) ;
  • Yoon, Sa-Rah (Department of Biochemistry and Molecular Biology, Yonsei University) ;
  • Moon, Jong-Seok (Department of Biochemistry and Molecular Biology, Yonsei University) ;
  • Park, Byeong-Woo (Institute of Genetic Science and Medical Research Center for Chronic Metabolic Disease, Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University) ;
  • Kim, Kyung-Sup (Department of Biochemistry and Molecular Biology, Yonsei University)
  • Published : 2008.10.31
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Abstract

Overexpression of HER2 in breast cancer cells is considered to induce the expression of acetyl-CoA carboxylase $\alpha$ (ACACA) and fatty acid synthase (FASN) through activation of mammalian target of rapamycin (mTOR) signaling pathway. Resveratrol, a red wine polyphenol, has been shown to induce apoptosis in several cancers by interfering in several signaling pathways. Present study elucidated the mechanism by which resveratrol downregulates ACACA and FASN in breast cancer cells. Resveratrol activated AMP-activated protein kinase (AMPK) and downregulated mTOR in BT-474 cells. These effects of resveratrol were mimicked by AICAR, an AMPK activator, and exogenously expressed constitutively active AMPK, while they were abolished by a dominant-negative mutant of AMPK. The downregulation of mTOR was not accompanied with changes in Akt, the upstream regulator of mTOR. These findings indicate that the downregulation of ACACA and FASN by resveratrol is mediated by the downregulation of mTOR signaling pathway via activation of AMPK.

Keywords

References

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