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Resveratrol Inhibits Proliferation and Induces Autophagy by Blocking SREBP1 Expression in Oral Cancer Cells

Resveratrol is a polyphenolic antioxidant found in grapes, red wine, and peanuts and has been reported to have anti-neoplastic effects on various cancer types. However, the exact mechanism of its anti-cancer effects in oral cancer is not fully understood and remains controversial. Resveratrol exhibi...

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Autores principales: Fukuda, Masakatsu, Ogasawara, Yudai, Hayashi, Hiroyasu, Inoue, Katsuyuki, Sakashita, Hideaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738393/
https://www.ncbi.nlm.nih.gov/pubmed/36500345
http://dx.doi.org/10.3390/molecules27238250
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author Fukuda, Masakatsu
Ogasawara, Yudai
Hayashi, Hiroyasu
Inoue, Katsuyuki
Sakashita, Hideaki
author_facet Fukuda, Masakatsu
Ogasawara, Yudai
Hayashi, Hiroyasu
Inoue, Katsuyuki
Sakashita, Hideaki
author_sort Fukuda, Masakatsu
collection PubMed
description Resveratrol is a polyphenolic antioxidant found in grapes, red wine, and peanuts and has been reported to have anti-neoplastic effects on various cancer types. However, the exact mechanism of its anti-cancer effects in oral cancer is not fully understood and remains controversial. Resveratrol exhibits strong hypolipidemic effects; therefore, we examined its effect on lipid metabolism in oral cancer. Resveratrol significantly reduced cell viability and induced autophagic cell death in oral cancer cells but not in normal cells. This selective effect was accompanied by significantly reduced lipogenesis, which is caused by downregulation of the transcription factor sterol regulatory element-binding protein 1 (SREBP1) gene, followed by downregulation of the epidermal fatty acid-binding protein (E-FABP). It was strongly suggested that resveratrol-induced autophagy resulted from the inhibition of SREBP1-mediated cell survival signaling. Luciferase reporter assay further indicated that resveratrol has a potent and specific inhibitory effect on SREBP1-dependent transactivation. Importantly, resveratrol markedly suppressed the growth of oral cancer cells in an animal xenograft model, without exhibiting apparent cytotoxicity. In conclusion, resveratrol induces autophagy in oral cancer cells by suppressing lipid metabolism through the regulation of SREBP1 expression, which highlights a novel mechanism of the anti-cancer effect of resveratrol.
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spelling pubmed-97383932022-12-11 Resveratrol Inhibits Proliferation and Induces Autophagy by Blocking SREBP1 Expression in Oral Cancer Cells Fukuda, Masakatsu Ogasawara, Yudai Hayashi, Hiroyasu Inoue, Katsuyuki Sakashita, Hideaki Molecules Article Resveratrol is a polyphenolic antioxidant found in grapes, red wine, and peanuts and has been reported to have anti-neoplastic effects on various cancer types. However, the exact mechanism of its anti-cancer effects in oral cancer is not fully understood and remains controversial. Resveratrol exhibits strong hypolipidemic effects; therefore, we examined its effect on lipid metabolism in oral cancer. Resveratrol significantly reduced cell viability and induced autophagic cell death in oral cancer cells but not in normal cells. This selective effect was accompanied by significantly reduced lipogenesis, which is caused by downregulation of the transcription factor sterol regulatory element-binding protein 1 (SREBP1) gene, followed by downregulation of the epidermal fatty acid-binding protein (E-FABP). It was strongly suggested that resveratrol-induced autophagy resulted from the inhibition of SREBP1-mediated cell survival signaling. Luciferase reporter assay further indicated that resveratrol has a potent and specific inhibitory effect on SREBP1-dependent transactivation. Importantly, resveratrol markedly suppressed the growth of oral cancer cells in an animal xenograft model, without exhibiting apparent cytotoxicity. In conclusion, resveratrol induces autophagy in oral cancer cells by suppressing lipid metabolism through the regulation of SREBP1 expression, which highlights a novel mechanism of the anti-cancer effect of resveratrol. MDPI 2022-11-26 /pmc/articles/PMC9738393/ /pubmed/36500345 http://dx.doi.org/10.3390/molecules27238250 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fukuda, Masakatsu
Ogasawara, Yudai
Hayashi, Hiroyasu
Inoue, Katsuyuki
Sakashita, Hideaki
Resveratrol Inhibits Proliferation and Induces Autophagy by Blocking SREBP1 Expression in Oral Cancer Cells
title Resveratrol Inhibits Proliferation and Induces Autophagy by Blocking SREBP1 Expression in Oral Cancer Cells
title_full Resveratrol Inhibits Proliferation and Induces Autophagy by Blocking SREBP1 Expression in Oral Cancer Cells
title_fullStr Resveratrol Inhibits Proliferation and Induces Autophagy by Blocking SREBP1 Expression in Oral Cancer Cells
title_full_unstemmed Resveratrol Inhibits Proliferation and Induces Autophagy by Blocking SREBP1 Expression in Oral Cancer Cells
title_short Resveratrol Inhibits Proliferation and Induces Autophagy by Blocking SREBP1 Expression in Oral Cancer Cells
title_sort resveratrol inhibits proliferation and induces autophagy by blocking srebp1 expression in oral cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738393/
https://www.ncbi.nlm.nih.gov/pubmed/36500345
http://dx.doi.org/10.3390/molecules27238250
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