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Resveratrol Downregulates Acetyl-CoA Carboxylase α and Fatty Acid Synthase by AMPK-mediated Downregulation of mTOR in Breast Cancer Cells

원문정보

Sahng Wook Park, Sarah Yoon, Jong-Seok Moon, Byeong-Woo Park, Kyung-Sup Kim

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초록

영어

Overexpression of HER2 in breast cancer cells is considered to induce the expression of acetyl-CoA carboxylase α (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.

목차

Abstract
 Introduction
 Materials and Methods
  Reagent
  Cell culture
  Cell viability assay
  Immunoblot analyses
  Reverse transcription (RT)-polymerase chain reaction(PCR)
 Results and Discussion
  Resveratrol decreases viability of breast cancer cellsoverexpressing HER2
  Effects of resveratrol on the expression of lipogenicenzymes and on activation of signaling molecules
  Resveratrol-mediated activation of AMPK downregulatesmTOR signaling pathway
 References

저자정보

  • Sahng Wook Park Department of Biochemistry and Molecular Biology, Yonsei University
  • Sarah Yoon Department of Biochemistry and Molecular Biology, Yonsei University, Institute of Genetic Science and Medical Research Center for Chronic Metabolic Disease Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University
  • Jong-Seok Moon Department of Biochemistry and Molecular Biology, Yonsei University, Institute of Genetic Science and Medical Research Center for Chronic Metabolic Disease Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University
  • Byeong-Woo Park Institute of Genetic Science and Medical Research Center for Chronic Metabolic Disease, Department of Surgery, College of Medicine, Yonsei University
  • Kyung-Sup Kim Department of Biochemistry and Molecular Biology, Yonsei University, Institute of Genetic Science and Medical Research Center for Chronic Metabolic Disease Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University

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