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Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells

Pancreatic cancer (PC) is one of the most aggressive human malignancies worldwide and is the fourth leading cause of cancer-related deaths. Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Certain studies have demonstrated that curcumin exerts its anti-tumor functio...

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Autores principales: Zhou, Xiuxia, Su, Jingna, Feng, Shaoyan, Wang, Lixia, Yin, Xuyuan, Yan, Jingzhe, Wang, Zhiwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346699/
https://www.ncbi.nlm.nih.gov/pubmed/27738325
http://dx.doi.org/10.18632/oncotarget.12596
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author Zhou, Xiuxia
Su, Jingna
Feng, Shaoyan
Wang, Lixia
Yin, Xuyuan
Yan, Jingzhe
Wang, Zhiwei
author_facet Zhou, Xiuxia
Su, Jingna
Feng, Shaoyan
Wang, Lixia
Yin, Xuyuan
Yan, Jingzhe
Wang, Zhiwei
author_sort Zhou, Xiuxia
collection PubMed
description Pancreatic cancer (PC) is one of the most aggressive human malignancies worldwide and is the fourth leading cause of cancer-related deaths. Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Certain studies have demonstrated that curcumin exerts its anti-tumor function in a variety of human cancers including PC, via targeting multiple therapeutically important cancer signaling pathways. However, the detailed molecular mechanisms are not fully understood. Two transcriptional co-activators, YAP (Yes-associated protein) and its close paralog TAZ (transcriptional coactivator with PDZ-binding motif) exert oncogenic activities in various cancers. Therefore, in this study we aimed to determine the molecular basis of curcumin-induced cell proliferation inhibition in PC cells. First, we detected the anti-tumor effects of curcumin on PC cell lines using CTG assay, Flow cytometry, clonogenic assay, wound healing assay and Transwell invasion assay. We found that curcumin significantly suppressed cell growth, weakened clonogenic potential, inhibited migration and invasion, and induced apoptosis and cell cycle arrest in PC cells. We further measured that overexpression of YAP enhanced cell proliferation and abrogated the cytotoxic effects of curcumin on PC cells. Moreover, we found that curcumin markedly down-regulated YAP and TAZ expression and subsequently suppressed Notch-1 expression. Collectively, these findings suggest that pharmacological inhibition of YAP and TAZ activity may be a promising anticancer strategy for the treatment of PC patients.
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spelling pubmed-53466992017-03-30 Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells Zhou, Xiuxia Su, Jingna Feng, Shaoyan Wang, Lixia Yin, Xuyuan Yan, Jingzhe Wang, Zhiwei Oncotarget Research Paper Pancreatic cancer (PC) is one of the most aggressive human malignancies worldwide and is the fourth leading cause of cancer-related deaths. Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Certain studies have demonstrated that curcumin exerts its anti-tumor function in a variety of human cancers including PC, via targeting multiple therapeutically important cancer signaling pathways. However, the detailed molecular mechanisms are not fully understood. Two transcriptional co-activators, YAP (Yes-associated protein) and its close paralog TAZ (transcriptional coactivator with PDZ-binding motif) exert oncogenic activities in various cancers. Therefore, in this study we aimed to determine the molecular basis of curcumin-induced cell proliferation inhibition in PC cells. First, we detected the anti-tumor effects of curcumin on PC cell lines using CTG assay, Flow cytometry, clonogenic assay, wound healing assay and Transwell invasion assay. We found that curcumin significantly suppressed cell growth, weakened clonogenic potential, inhibited migration and invasion, and induced apoptosis and cell cycle arrest in PC cells. We further measured that overexpression of YAP enhanced cell proliferation and abrogated the cytotoxic effects of curcumin on PC cells. Moreover, we found that curcumin markedly down-regulated YAP and TAZ expression and subsequently suppressed Notch-1 expression. Collectively, these findings suggest that pharmacological inhibition of YAP and TAZ activity may be a promising anticancer strategy for the treatment of PC patients. Impact Journals LLC 2016-10-12 /pmc/articles/PMC5346699/ /pubmed/27738325 http://dx.doi.org/10.18632/oncotarget.12596 Text en Copyright: © 2016 Zhou 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
Zhou, Xiuxia
Su, Jingna
Feng, Shaoyan
Wang, Lixia
Yin, Xuyuan
Yan, Jingzhe
Wang, Zhiwei
Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells
title Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells
title_full Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells
title_fullStr Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells
title_full_unstemmed Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells
title_short Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells
title_sort antitumor activity of curcumin is involved in down-regulation of yap/taz expression in pancreatic cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346699/
https://www.ncbi.nlm.nih.gov/pubmed/27738325
http://dx.doi.org/10.18632/oncotarget.12596
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