Cai Shi-Zhong, Xiong Qian-Wei, Zhao Li-Na, Ji Yi-Ting, Luo Zheng-Xiang, Ma Zhou-Rui
Department of Child and Adolescent Healthcare, Children's Hospital of Soochow University, Suzhou, China.
Department of Surgery, Children's Hospital of Soochow University, Suzhou, China.
Pathol Oncol Res. 2021 Mar 25;27:594299. doi: 10.3389/pore.2021.594299. eCollection 2021.
Glioblastoma is one of the most aggressive primary brain tumors with few treatment strategies. β-Elemene is a sesquiterpene known to have broad spectrum antitumor activity against various cancers. However, the signaling pathways involved in β-elemene induced apoptosis of glioblastoma cells remains poorly understood. In this study, we reported that β-elemene exhibited antiproliferative activity on U87 and SHG-44 cells, and induced cell death through induction of apoptosis. Incubation of these cells with β-elemene led to the activation of caspase-3 and generation of reactive oxygen species (ROS). Western blot assay showed that β-elemene suppressed phosphorylation of STAT3, and subsequently down-regulated the activation of -JAK2 and -Src. Moreover, pre-incubation of cells with ROS inhibitor -acetyl--cysteine (NAC) significantly reversed β-elemene-mediated apoptosis effect and down-regulation of JAK2/Src-STAT3 signaling pathway. Overall, our findings implied that generation of ROS and suppression of STAT3 signaling pathway is critical for the apoptotic activity of β-elemene in glioblastoma cells.
胶质母细胞瘤是最具侵袭性的原发性脑肿瘤之一，治疗策略有限。β-榄香烯是一种倍半萜烯，已知对多种癌症具有广谱抗肿瘤活性。然而，β-榄香烯诱导胶质母细胞瘤细胞凋亡所涉及的信号通路仍知之甚少。在本研究中，我们报道β-榄香烯对U87和SHG-44细胞具有抗增殖活性，并通过诱导凋亡导致细胞死亡。用β-榄香烯处理这些细胞导致caspase-3激活和活性氧（ROS）生成。蛋白质印迹分析表明，β-榄香烯抑制STAT3磷酸化，随后下调JAK2和Src的激活。此外，用ROS抑制剂N-乙酰-L-半胱氨酸（NAC）预先处理细胞可显著逆转β-榄香烯介导的凋亡效应以及JAK2/Src-STAT3信号通路的下调。总体而言，我们的研究结果表明，ROS的生成和STAT3信号通路的抑制对于β-榄香烯在胶质母细胞瘤细胞中的凋亡活性至关重要。
