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The Selective Target of Capsaicin on FASN Expression and De Novo Fatty Acid Synthesis Mediated through ROS Generation Triggers Apoptosis in HepG2 Cells

The inhibition of the mammalian de novo synthesis of long-chain saturated fatty acids (LCFAs) by blocking the fatty acid synthase (FASN) enzyme activity in tumor cells that overexpress FASN can promote apoptosis, without apparent cytotoxic to non-tumor cells. The present study aimed to focus on the...

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Autores principales: Impheng, Hathaichanok, Pongcharoen, Sutatip, Richert, Lysiane, Pekthong, Dumrongsak, Srisawang, Piyarat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177889/
https://www.ncbi.nlm.nih.gov/pubmed/25255125
http://dx.doi.org/10.1371/journal.pone.0107842
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author Impheng, Hathaichanok
Pongcharoen, Sutatip
Richert, Lysiane
Pekthong, Dumrongsak
Srisawang, Piyarat
author_facet Impheng, Hathaichanok
Pongcharoen, Sutatip
Richert, Lysiane
Pekthong, Dumrongsak
Srisawang, Piyarat
author_sort Impheng, Hathaichanok
collection PubMed
description The inhibition of the mammalian de novo synthesis of long-chain saturated fatty acids (LCFAs) by blocking the fatty acid synthase (FASN) enzyme activity in tumor cells that overexpress FASN can promote apoptosis, without apparent cytotoxic to non-tumor cells. The present study aimed to focus on the potent inhibitory effect of capsaicin on the fatty acid synthesis pathway inducing apoptosis of capsaicin in HepG2 cells. The use of capsaicin as a source for a new FASN inhibitor will provide new insight into its possible application as a selective anti-cancer therapy. The present findings showed that capsaicin promoted apoptosis as well as cell cycle arrest in the G0/G1 phase. The onset of apoptosis was correlated with a dissipation of mitochondrial membrane potential (ΔΨm). Apoptotic induction by capsaicin was mediated by inhibition of FASN protein expression which was accompanied by decreasing its activity on the de novo fatty acid synthesis. The expression of FASN was higher in HepG2 cells than in normal hepatocytes that were resistant to undergoing apoptosis following capsaicin administration. Moreover, the inhibitory effect of capsaicin on FASN expression and activity was found to be mediated by an increase of intracellular reactive oxygen species (ROS) generation. Treatment of HepG2 cells with capsaicin failed to alter ACC and ACLY protein expression, suggesting ACC and ACLY might not be the specific targets of capsaicin to induce apoptosis. An accumulation of malonyl-CoA level following FASN inhibition represented a major cause of mitochondrial-dependent apoptotic induction instead of deprivation of fatty acid per se. Here, we also obtained similar results with C75 that exhibited apoptosis induction by reducing the levels of fatty acid without any change in the abundance of FASN expression along with increasing ROS production. Collectively, our results provide novel evidence that capsaicin exhibits a potent anti-cancer property by targeting FASN protein in HepG2 cells.
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spelling pubmed-41778892014-10-02 The Selective Target of Capsaicin on FASN Expression and De Novo Fatty Acid Synthesis Mediated through ROS Generation Triggers Apoptosis in HepG2 Cells Impheng, Hathaichanok Pongcharoen, Sutatip Richert, Lysiane Pekthong, Dumrongsak Srisawang, Piyarat PLoS One Research Article The inhibition of the mammalian de novo synthesis of long-chain saturated fatty acids (LCFAs) by blocking the fatty acid synthase (FASN) enzyme activity in tumor cells that overexpress FASN can promote apoptosis, without apparent cytotoxic to non-tumor cells. The present study aimed to focus on the potent inhibitory effect of capsaicin on the fatty acid synthesis pathway inducing apoptosis of capsaicin in HepG2 cells. The use of capsaicin as a source for a new FASN inhibitor will provide new insight into its possible application as a selective anti-cancer therapy. The present findings showed that capsaicin promoted apoptosis as well as cell cycle arrest in the G0/G1 phase. The onset of apoptosis was correlated with a dissipation of mitochondrial membrane potential (ΔΨm). Apoptotic induction by capsaicin was mediated by inhibition of FASN protein expression which was accompanied by decreasing its activity on the de novo fatty acid synthesis. The expression of FASN was higher in HepG2 cells than in normal hepatocytes that were resistant to undergoing apoptosis following capsaicin administration. Moreover, the inhibitory effect of capsaicin on FASN expression and activity was found to be mediated by an increase of intracellular reactive oxygen species (ROS) generation. Treatment of HepG2 cells with capsaicin failed to alter ACC and ACLY protein expression, suggesting ACC and ACLY might not be the specific targets of capsaicin to induce apoptosis. An accumulation of malonyl-CoA level following FASN inhibition represented a major cause of mitochondrial-dependent apoptotic induction instead of deprivation of fatty acid per se. Here, we also obtained similar results with C75 that exhibited apoptosis induction by reducing the levels of fatty acid without any change in the abundance of FASN expression along with increasing ROS production. Collectively, our results provide novel evidence that capsaicin exhibits a potent anti-cancer property by targeting FASN protein in HepG2 cells. Public Library of Science 2014-09-25 /pmc/articles/PMC4177889/ /pubmed/25255125 http://dx.doi.org/10.1371/journal.pone.0107842 Text en © 2014 Impheng et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Impheng, Hathaichanok
Pongcharoen, Sutatip
Richert, Lysiane
Pekthong, Dumrongsak
Srisawang, Piyarat
The Selective Target of Capsaicin on FASN Expression and De Novo Fatty Acid Synthesis Mediated through ROS Generation Triggers Apoptosis in HepG2 Cells
title The Selective Target of Capsaicin on FASN Expression and De Novo Fatty Acid Synthesis Mediated through ROS Generation Triggers Apoptosis in HepG2 Cells
title_full The Selective Target of Capsaicin on FASN Expression and De Novo Fatty Acid Synthesis Mediated through ROS Generation Triggers Apoptosis in HepG2 Cells
title_fullStr The Selective Target of Capsaicin on FASN Expression and De Novo Fatty Acid Synthesis Mediated through ROS Generation Triggers Apoptosis in HepG2 Cells
title_full_unstemmed The Selective Target of Capsaicin on FASN Expression and De Novo Fatty Acid Synthesis Mediated through ROS Generation Triggers Apoptosis in HepG2 Cells
title_short The Selective Target of Capsaicin on FASN Expression and De Novo Fatty Acid Synthesis Mediated through ROS Generation Triggers Apoptosis in HepG2 Cells
title_sort selective target of capsaicin on fasn expression and de novo fatty acid synthesis mediated through ros generation triggers apoptosis in hepg2 cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177889/
https://www.ncbi.nlm.nih.gov/pubmed/25255125
http://dx.doi.org/10.1371/journal.pone.0107842
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