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Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines

Fisetin was reported to have an anti-proliferative and apoptotic activity as a novel anti-cancer agent in various cancer cell lines. However, the possible molecular targets for the anti-cancer effect of fisetin in human head and neck cancer (HNCC) have not yet been clarified. In this study, the infl...

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Autores principales: Won, Dong-Hoon, Chung, Shin Hye, Shin, Ji-Ae, Hong, Kyoung-Ok, Yang, In-Hyoung, Yun, Jun-Won, Cho, Sung-Dae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: the Society for Free Radical Research Japan 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436036/
https://www.ncbi.nlm.nih.gov/pubmed/30936621
http://dx.doi.org/10.3164/jcbn.18-63
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author Won, Dong-Hoon
Chung, Shin Hye
Shin, Ji-Ae
Hong, Kyoung-Ok
Yang, In-Hyoung
Yun, Jun-Won
Cho, Sung-Dae
author_facet Won, Dong-Hoon
Chung, Shin Hye
Shin, Ji-Ae
Hong, Kyoung-Ok
Yang, In-Hyoung
Yun, Jun-Won
Cho, Sung-Dae
author_sort Won, Dong-Hoon
collection PubMed
description Fisetin was reported to have an anti-proliferative and apoptotic activity as a novel anti-cancer agent in various cancer cell lines. However, the possible molecular targets for the anti-cancer effect of fisetin in human head and neck cancer (HNCC) have not yet been clarified. In this study, the influence of fisetin on the growth and apoptosis of HNCCs were examined. In HSC3 cells, fisetin treatment reduced the viability and induced apoptosis. Through the results from the screening of the expression profile of apoptosis-related genes, sestrin 2 (SESN2) was functionally involved in fisetin-mediated apoptosis showing the knockdown of SESN2 by siRNA clearly restored fisetin-induced apoptosis. In addition, fisetin reduced the protein expression levels of phospho-mTOR (p-mTOR) and Mcl-1, which are the downstream molecules of SESN2. It also induced PARP cleavage by inducing an increase in the expression levels of SESN2 together with reducing mTOR and Mcl-1 proteins in other three HNCCs (MC3, Ca9.22, and HN22). Taken together, our findings suggest that the anti-cancer effect of fisetin on HNCCs is associated with SESN2/mTOR/Mcl-1 signaling axis.
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spelling pubmed-64360362019-04-01 Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines Won, Dong-Hoon Chung, Shin Hye Shin, Ji-Ae Hong, Kyoung-Ok Yang, In-Hyoung Yun, Jun-Won Cho, Sung-Dae J Clin Biochem Nutr Original Article Fisetin was reported to have an anti-proliferative and apoptotic activity as a novel anti-cancer agent in various cancer cell lines. However, the possible molecular targets for the anti-cancer effect of fisetin in human head and neck cancer (HNCC) have not yet been clarified. In this study, the influence of fisetin on the growth and apoptosis of HNCCs were examined. In HSC3 cells, fisetin treatment reduced the viability and induced apoptosis. Through the results from the screening of the expression profile of apoptosis-related genes, sestrin 2 (SESN2) was functionally involved in fisetin-mediated apoptosis showing the knockdown of SESN2 by siRNA clearly restored fisetin-induced apoptosis. In addition, fisetin reduced the protein expression levels of phospho-mTOR (p-mTOR) and Mcl-1, which are the downstream molecules of SESN2. It also induced PARP cleavage by inducing an increase in the expression levels of SESN2 together with reducing mTOR and Mcl-1 proteins in other three HNCCs (MC3, Ca9.22, and HN22). Taken together, our findings suggest that the anti-cancer effect of fisetin on HNCCs is associated with SESN2/mTOR/Mcl-1 signaling axis. the Society for Free Radical Research Japan 2019-03 2018-10-13 /pmc/articles/PMC6436036/ /pubmed/30936621 http://dx.doi.org/10.3164/jcbn.18-63 Text en Copyright © 2018 JCBN http://creativecommons.org/licenses/by/3.0/ 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 work is properly cited.
spellingShingle Original Article
Won, Dong-Hoon
Chung, Shin Hye
Shin, Ji-Ae
Hong, Kyoung-Ok
Yang, In-Hyoung
Yun, Jun-Won
Cho, Sung-Dae
Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines
title Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines
title_full Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines
title_fullStr Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines
title_full_unstemmed Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines
title_short Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines
title_sort induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436036/
https://www.ncbi.nlm.nih.gov/pubmed/30936621
http://dx.doi.org/10.3164/jcbn.18-63
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