Afshari Amir R, Karimi Roshan Mostafa, Soukhtanloo Mohammad, Ghorbani Ahmad, Rahmani Farzad, Jalili-Nik Mohammad, Vahedi Mohammad Mahdi, Hoseini Azar, Sadeghnia Hamid R, Mollazadeh Hamid, Mousavi Seyed Hadi
Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.
Avicenna J Phytomed. 2019 Jul-Aug;9(4):334-346.
Glioblastoma multiforme (GBM) is the deadliest type of primary brain tumors, and the survival of patients is estimated to be only about one year. This study, for the first time, investigated the cytotoxic effects of auraptene on U87 GBM cell line.
The cellular toxicity was measured by the MTT assay following 24 and 48-hr treatment with different concentrations of auraptene (0-400μg/ml). Apoptosis was evaluated by sub-G1 peak in cell cycle analysis of propidium-iodide- stained nuclei. Moreover, to determine the Ba, , , , , and genes expression, we used real-time polymerase chain reaction (RT-PCR).
The results revealed that auraptene reduced the viability of U87 cells concentration- and time-dependently with IC values of 108.9 and 79.17μg/ml obtained for 24 and 48-hr treatments, respectively. Also, sub-G1 population was significantly increased following 24 (p<0.05 and p<0.001) and 48 (p<0.001) hours of treatment. The quantitative real-time RT-PCR showed an up-regulation in , , , and but a down-regulation in and genes expression.
This study showed that auraptene triggered apoptosis probably through Bax/Bcl-2 regulation, blocked cell cycle progression and inhibited proliferation in U87 GBM cells. Taken together, auraptene can be utilized as an effective natural medicine against GBM, after complementary studies.
多形性胶质母细胞瘤（GBM）是最致命的原发性脑肿瘤类型，患者的生存期估计仅约一年。本研究首次调查了金雀异黄素对U87 GBM细胞系的细胞毒性作用。
用不同浓度的金雀异黄素（0 - 400μg/ml）处理24小时和48小时后，通过MTT法测定细胞毒性。通过碘化丙啶染色细胞核的细胞周期分析中的亚G1峰评估细胞凋亡。此外，为了确定Ba、、、、和基因的表达，我们使用了实时聚合酶链反应（RT-PCR）。
结果显示，金雀异黄素浓度和时间依赖性地降低了U87细胞的活力，24小时和48小时处理的IC值分别为108.9和79.17μg/ml。此外，处理24小时（p<0.05和p<0.001）和48小时（p<0.001）后，亚G1期细胞群体显著增加。定量实时RT-PCR显示、、、基因表达上调，而和基因表达下调。
本研究表明，金雀异黄素可能通过Bax/Bcl-2调节触发细胞凋亡，阻断细胞周期进程并抑制U87 GBM细胞的增殖。综上所述，经过补充研究后，金雀异黄素可作为一种有效的抗GBM天然药物。
