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Resveratrol Induces Cell Death through ROS-dependent MAPK Activation in A172 Human Glioma Cells

사람의 신경교모세포종 기원 세포에서 레스베라트롤에 의한 활성산소종 생성 증가와 MAPK 활성화를 통한 세포 사멸 효과

Jung, Jung Suk;Woo, Jae Suk
정정숙;우재석

  • Received : 2015.12.14
  • Accepted : 2016.01.28
  • Published : 2016.02.25

Abstract

Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor in humans. Despite intensive treatment, including surgery, radiation, and chemotherapy, most patients die of the disease. Although the anti-cancer activity of resveratrol has been demonstrated in various cancer cell types, its underlying mechanism in glioma cells is not fully elucidated. The present study was undertaken to investigate the effect of resveratrol on cell viability and to determine the molecular mechanism in A172 human glioma cells. Resveratrol caused the generation of reactive oxygen species (ROS), and resveratrol-induced cell death was prevented by antioxidants (N-acetylcysteine and catalase), suggesting that an oxidative mechanism is responsible for resveratrol-induced cell death. Resveratrol-induced phosphorylation of extracellular signal-regulated kinase (ERK), p38 kinase, and c-Jun N-terminal kinase (JNK), and resveratrol-induced cell death were prevented by inhibitors of these kinases. Resveratrol-induced activation of caspase-3 and cell death were prevented by the caspase inhibitors. ERK activation and caspase-3 activation induced by resveratrol was blocked by N-acetylcysteine. Taken together, these results suggest that resveratrol causes a caspase-dependent cell death via activation of ERK, p38, and JNK, mediated by ROS generation, in human glioma cells.

Keywords

Cell viability;glioma cells;MAPK;resveratrol;reactive oxygen species

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