Resveratrol downregulates acetyl-CoA carboxylase α and fatty acid synthase by AMPK-mediated downregulation of mTOR in breast cancer cells

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1047-1051
Number of pages5
JournalFood Science and Biotechnology
Volume17
Issue number5
Publication statusPublished - 2008 Nov 21

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Acetyl-CoA Carboxylase
AMP-activated protein kinase
Fatty Acid Synthases
acetyl-CoA carboxylase
fatty-acid synthase
AMP-Activated Protein Kinases
resveratrol
Sirolimus
breast neoplasms
Down-Regulation
Breast Neoplasms
Polyphenols
Wine
red wines
polyphenols
apoptosis
neoplasm cells
Apoptosis
mutants
neoplasms

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Food Science
  • Applied Microbiology and Biotechnology

Cite this

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title = "Resveratrol downregulates acetyl-CoA carboxylase α and fatty acid synthase by AMPK-mediated downregulation of mTOR in breast cancer cells",
abstract = "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.",
author = "Sahng, {Wook Park} and Sarah Yoon and Moon, {Jong Seok} and Park, {Byeong Woo} and Kim, {Kyung Sup}",
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Resveratrol downregulates acetyl-CoA carboxylase α and fatty acid synthase by AMPK-mediated downregulation of mTOR in breast cancer cells. / Sahng, Wook Park; Yoon, Sarah; Moon, Jong Seok; Park, Byeong Woo; Kim, Kyung Sup.

In: Food Science and Biotechnology, Vol. 17, No. 5, 21.11.2008, p. 1047-1051.

Research output: Contribution to journalArticle

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AU - Yoon, Sarah

AU - Moon, Jong Seok

AU - Park, Byeong Woo

AU - Kim, Kyung Sup

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AB - 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.

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