Resveratrol enhances the therapeutic effect of temozolomide against malignant glioma in vitro and in vivo by inhibiting autophagy

Chien Ju Lin, Chin-Cheng Lee, Yung Luen Shih, Tsung Yao Lin, Sheng Hao Wang, Yuh Feng Lin, Chwen Ming Shih

研究成果: 雜誌貢獻文章同行評審

150 引文 斯高帕斯(Scopus)

摘要

The alkylating agent temozolomide (TMZ) is the major chemotherapeutic drug used clinically in the treatment of malignant gliomas. This study investigated the mechanism behind TMZ-induced cell death and the possibility that resveratrol might increase TMZ efficacy. TMZ induced both apoptotic cell death and cytoprotective autophagy through a reactive oxygen species (ROS) burst and extracellular signal-regulated kinase (ERK) activation, which was suppressed by resveratrol, resulting in a decrease in autophagy and an increase in apoptosis, suggesting that the ROS/ERK pathway plays a crucial role in the fate of cells after TMZ treatment. Isobolographic analysis indicated that the combination of TMZ and resveratrol has a synergistic effect. Moreover, an in vivo mouse xenograft study also showed that coadministration of resveratrol and TMZ reduced tumor volumes by suppressing ROS/ERK-mediated autophagy and subsequently inducing apoptosis. Taken together, our data indicate that TMZ-induced ROS/ERK-mediated autophagy protected glioma cells from apoptosis, and the combination of resveratrol with TMZ could improve the efficacy of chemotherapy for brain tumors.

原文英語
頁(從 - 到)377-391
頁數15
期刊Free Radical Biology and Medicine
52
發行號2
DOIs
出版狀態已發佈 - 1月 15 2012

ASJC Scopus subject areas

  • 生物化學
  • 生理學(醫學)

指紋

深入研究「Resveratrol enhances the therapeutic effect of temozolomide against malignant glioma in vitro and in vivo by inhibiting autophagy」主題。共同形成了獨特的指紋。

引用此