J Cancer 2021; 12(1):141-149. doi:10.7150/jca.45489

Research Paper

Increased Reactive Oxygen Species and Distinct Oxidative Damage in Resveratrol-suppressed Glioblastoma Cells

Bin Jia1*, Xu Zheng1*, Mo-Li Wu1, Xiao-Ting Tian1, Xue Song1, Yan-Na Liu1, Pei-Nan Li2✉, Jia Liu1✉

1. Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
2. Department of Orthopaedic Surgery, Second Affiliated Hospital, Dalian Medical University, Dalian 116011, China.
*Equal contributions as co-first authors.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Jia B, Zheng X, Wu ML, Tian XT, Song X, Liu YN, Li PN, Liu J. Increased Reactive Oxygen Species and Distinct Oxidative Damage in Resveratrol-suppressed Glioblastoma Cells. J Cancer 2021; 12(1):141-149. doi:10.7150/jca.45489. Available from https://www.jcancer.org/v12p0141.htm

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Background and Aim: Glioblastoma multiforme (GBM) is a highly aggressive brain malignancy that lacks reliable treatments. Resveratrol possesses anti-cancer effects, but its activity against glioblastoma cells is variable for unknown reasons. One mechanism through which anti-cancer drugs exert their effects is oxidative damage caused by increased reactive oxygen species (ROS) production. Thus, the present study examined the relationship between oxidative stress and sensitivity to resveratrol in glioblastoma cells.

Methods: Two GBM cell lines (U251 and LN428) were exposed to 100 μM resveratrol for 48 h, and proliferation and apoptosis were assessed. ROS generation was evaluated using 2′-7′-dichlorodihydrofluorescein diacetate-based flow cytometry and fluorescent microscopy. Immunocytochemical staining and western blotting were conducted at regular intervals to profile the expression patterns of superoxide dismutase-2 (SOD2), catalase, caspase-9, caspase-3, and sulfotransferases (SULTs) in untreated and resveratrol-treated GBM cells.

Results: Resveratrol-treated U251 cells, but not resveratrol-treated LN428 cells, exhibited remarkable growth arrest and extensive apoptosis accompanied by elevated intracellular ROS levels and attenuated SOD2 and catalase expression. Mitochondrial impairment and more distinct increases in the expression of activated caspase-9 and caspase-3 were detected in U251 cells following resveratrol treatment. The levels of resveratrol metabolic enzymes (SULT1A1 and SULT1C2) were lower in U251 cells than in LN428 cells.

Conclusions: Resveratrol increased ROS generation and induced oxidation-related cellular lesions in U251 cells by activating an ROS-related mitochondrial signal pathway. The levels of SULTs and ROS may indicate the therapeutic outcomes of resveratrol treatment in GBM.

Keywords: resveratrol, glioblastoma multiforme, reactive oxygen species, oxidative activity, mitochondrial damage