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Curcumin targets the TFEB-lysosome pathway for induction of autophagy

Curcumin is a hydrophobic polyphenol derived from the herb Curcumalonga and its wide spectrum of pharmacological activities has been widely studied. It has been reported that Curcumin can induce autophagy through inhibition of the Akt-mTOR pathway. However, the effect of Curcumin on lysosome remains...

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Autores principales: Zhang, Jianbin, Wang, Jigang, Xu, Jian, Lu, Yuanqiang, Jiang, Jiukun, Wang, Liming, Shen, Han-Ming, Xia, Dajing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342768/
https://www.ncbi.nlm.nih.gov/pubmed/27689333
http://dx.doi.org/10.18632/oncotarget.12318
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author Zhang, Jianbin
Wang, Jigang
Xu, Jian
Lu, Yuanqiang
Jiang, Jiukun
Wang, Liming
Shen, Han-Ming
Xia, Dajing
author_facet Zhang, Jianbin
Wang, Jigang
Xu, Jian
Lu, Yuanqiang
Jiang, Jiukun
Wang, Liming
Shen, Han-Ming
Xia, Dajing
author_sort Zhang, Jianbin
collection PubMed
description Curcumin is a hydrophobic polyphenol derived from the herb Curcumalonga and its wide spectrum of pharmacological activities has been widely studied. It has been reported that Curcumin can induce autophagy through inhibition of the Akt-mTOR pathway. However, the effect of Curcumin on lysosome remains largely elusive. In this study, we first found that Curcumin treatment enhances autophagic flux in both human colon cancer HCT116 cells and mouse embryonic fibroblasts (MEFs). Moreover, Curcumin treatment promotes lysosomal function, evidenced by the increased lysosomal acidification and enzyme activity. Second, Curcumin is capable of suppressing the mammalian target of rapamycin (mTOR). Interestingly, Curcumin fails to inhibit mTOR and to activate lysosomal function in Tsc2(−/−)MEFs with constitutive activation of mTOR, indicating that Curcumin-mediated lysosomal activation is achieved via suppression of mTOR. Third, Curcumin treatment activates transcription factor EB (TFEB), a key nuclear transcription factor in control of autophagy and lysosome biogenesis and function, based on the following observations: (i) Curcumin directly binds to TFEB, (ii) Curcumin promotes TFEB nuclear translocation; and (iii) Curcumin increases transcriptional activity of TFEB. Finally, inhibition of autophagy and lysosome leads to more cell death in Curcumin-treated HCT116 cells, suggesting that autophagy and lysosomal activation serves as a cell survival mechanism to protect against Curcumin-mediated cell death. Taken together, data from our study provide a novel insight into the regulatory mechanisms of Curcumin on autophagy and lysosome, which may facilitate the development of Curcumin as a potential cancer therapeutic agent.
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spelling pubmed-53427682017-03-28 Curcumin targets the TFEB-lysosome pathway for induction of autophagy Zhang, Jianbin Wang, Jigang Xu, Jian Lu, Yuanqiang Jiang, Jiukun Wang, Liming Shen, Han-Ming Xia, Dajing Oncotarget Research Paper Curcumin is a hydrophobic polyphenol derived from the herb Curcumalonga and its wide spectrum of pharmacological activities has been widely studied. It has been reported that Curcumin can induce autophagy through inhibition of the Akt-mTOR pathway. However, the effect of Curcumin on lysosome remains largely elusive. In this study, we first found that Curcumin treatment enhances autophagic flux in both human colon cancer HCT116 cells and mouse embryonic fibroblasts (MEFs). Moreover, Curcumin treatment promotes lysosomal function, evidenced by the increased lysosomal acidification and enzyme activity. Second, Curcumin is capable of suppressing the mammalian target of rapamycin (mTOR). Interestingly, Curcumin fails to inhibit mTOR and to activate lysosomal function in Tsc2(−/−)MEFs with constitutive activation of mTOR, indicating that Curcumin-mediated lysosomal activation is achieved via suppression of mTOR. Third, Curcumin treatment activates transcription factor EB (TFEB), a key nuclear transcription factor in control of autophagy and lysosome biogenesis and function, based on the following observations: (i) Curcumin directly binds to TFEB, (ii) Curcumin promotes TFEB nuclear translocation; and (iii) Curcumin increases transcriptional activity of TFEB. Finally, inhibition of autophagy and lysosome leads to more cell death in Curcumin-treated HCT116 cells, suggesting that autophagy and lysosomal activation serves as a cell survival mechanism to protect against Curcumin-mediated cell death. Taken together, data from our study provide a novel insight into the regulatory mechanisms of Curcumin on autophagy and lysosome, which may facilitate the development of Curcumin as a potential cancer therapeutic agent. Impact Journals LLC 2016-09-28 /pmc/articles/PMC5342768/ /pubmed/27689333 http://dx.doi.org/10.18632/oncotarget.12318 Text en Copyright: © 2016 Zhang et al. 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 author and source are credited.
spellingShingle Research Paper
Zhang, Jianbin
Wang, Jigang
Xu, Jian
Lu, Yuanqiang
Jiang, Jiukun
Wang, Liming
Shen, Han-Ming
Xia, Dajing
Curcumin targets the TFEB-lysosome pathway for induction of autophagy
title Curcumin targets the TFEB-lysosome pathway for induction of autophagy
title_full Curcumin targets the TFEB-lysosome pathway for induction of autophagy
title_fullStr Curcumin targets the TFEB-lysosome pathway for induction of autophagy
title_full_unstemmed Curcumin targets the TFEB-lysosome pathway for induction of autophagy
title_short Curcumin targets the TFEB-lysosome pathway for induction of autophagy
title_sort curcumin targets the tfeb-lysosome pathway for induction of autophagy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342768/
https://www.ncbi.nlm.nih.gov/pubmed/27689333
http://dx.doi.org/10.18632/oncotarget.12318
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