Resveratrol sensitizes glioblastoma-initiating cells to temozolomide by inducing cell apoptosis and promoting differentiation

Li,Hao; Liu,Yaodong; Jiao,Yumin; Guo,Anchen; Xu,Xiaoxue; Qu,Xianjun; Wang,Shuo; Zhao,Jizong; Li,Ye; Cao,Yong

doi:10.3892/or.2015.4346

Resveratrol sensitizes glioblastoma-initiating cells to temozolomide by inducing cell apoptosis and promoting differentiation

Authors:
- Hao Li
- Yaodong Liu
- Yumin Jiao
- Anchen Guo
- Xiaoxue Xu
- Xianjun Qu
- Shuo Wang
- Jizong Zhao
- Ye Li
- Yong Cao
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Affiliations: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China, China National Clinical Research Center for Neurological Diseases, Beijing 100050, P.R. China, Medical Experiments and Testing Center, Capital Medical University, Beijing 100069, P.R. China, Department of Pharmacology, School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing 100069, P.R. China
Published online on: October 23, 2015 https://doi.org/10.3892/or.2015.4346
Pages: 343-351

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Abstract

Glioblastoma-initiating cells play crucial roles in the origin, growth, and recurrence of glioblastoma multiforme. The elimination of glioblastoma-initiating cells is believed to be a key strategy for achieving long-term survival of glioblastoma patients due to the highly resistant property of glioblastoma‑initiating cells to temozolomide. Resveratrol, a naturally occurring polyphenol, has been widely studied as a promising candidate for cancer prevention and treatment. Whether resveratrol could enhance the sensitivity of glioblastoma-initiating cells to temozolomide therapy has not yet been reported. Here, using patient-derived glioblastoma-initiating cell lines, we found that resveratrol sensitized glioblastoma-initiating cells to temozolomide both in vitro and in vivo. Furthermore, we showed that resveratrol enhanced glioblastoma-initiating cells to temozolomide-induced apoptosis through DNA double‑stranded breaks/pATM/pATR/p53 pathway activation, and promoted glioblastoma-initiating cell differentiation involving p-STAT3 inactivation. Our results propose that temozolomide and resveratrol combination strategy may be effective in the management of glioblastoma patients, particularly for those patients who have been present with a high abundance of glioblastoma-initiating cells in their tumors and show slight responsiveness to temozolomide.

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