Resveratrol impedes the stemness, epithelial-mesenchymal transition, and metabolic reprogramming of cancer stem cells in nasopharyngeal carcinoma through p53 activation

Yao An Shen, Chien Hung Lin, Wei Hsin Chi, Chia Yu Wang, Yi Tao Hsieh, Yau Huei Wei*, Yann Jang Chen

*此作品的通信作者

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72 引文 斯高帕斯(Scopus)

摘要

Cancer stem cells (CSCs) are able to self-renew and are refractory to cancer treatment. To investigate the effects of resveratrol on CSCs of nasopharyngeal carcinoma (NPC), we employed a behavior selection strategy to isolate CSCs based on radioresistance, chemoresistance, and tumor sphere formation ability. These NPC CSCs displayed stem cell properties and underwent metabolic shift to predominately rely on glycolysis for energy supply. Intriguingly, we found that resveratrol turned off the metabolic switch, increased the reactive oxygen species (ROS) level, and depolarized mitochondrial membranes. These alterations in metabolism occurred concomitantly with the suppression of CSC properties including resistance to therapy, self-renewal capacity, tumor initiation capacity, and metastatic potential in NPC CSCs. We found that resveratrol impeded CSC properties through the activation of p53 and this effect could be reversed by knockdown of p53. Furthermore, resveratrol suppressed the stemness and EMT through reactivating p53 and inducing miR-145 and miR-200c, which were downregulated in NPC CSCs. In conclusion, we demonstrated that resveratrol employed the p53 pathway in regulating stemness, EMT, and metabolic reprogramming. Further investigation of the molecular mechanism of p53 activation by resveratrol may provide useful information for the development of novel therapies for cancer treatment through targeting to CSCs.

原文English
文章編號590393
期刊Evidence-based Complementary and Alternative Medicine
2013
DOIs
出版狀態Published - 2013

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