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山奈酚通过诱导程序性细胞死亡发挥抗胶质母细胞瘤活性:自噬和焦亡的参与

Anti-glioblastoma Activity of Kaempferol via Programmed Cell Death Induction: Involvement of Autophagy and Pyroptosis.

作者信息

Chen Suqin, Ma Jing, Yang Liu, Teng Muzhou, Lai Zheng-Quan, Chen Xiaoyu, He Jingjin

机构信息

The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

出版信息

Front Bioeng Biotechnol. 2020 Dec 10;8:614419. doi: 10.3389/fbioe.2020.614419. eCollection 2020.

Abstract

Glioblastoma is one of the most common and lethal intracranial malignant, and is still lack of ideal treatments. Kaempferol is a major nutrient found in various edible plants, which has exhibited the potential for the treatment of glioblastoma. However, the specific anti-glioma mechanism of kaempferol is yet to be studied. Herein, we aim to explore the mechanisms underlying the anti-glioma activity of kaempferol. Our results demonstrated that kaempferol suppresses glioma cell proliferation and inhibits tumor growth . Moreover, kaempferol raises ROS and decreases mitochondrial membrane potential in glioma cells. The high levels of ROS induce autophagy then ultimately trigger the pyroptosis of glioma cells. Interestingly, when we used 3-MA to inhibit autophagy, we found that the cleaved form of GSDME was also decreased, suggesting that kaempferol induces pyroptosis through regulating autophagy in glioma cells. In conclusion, this study revealed kaempferol possesses good anti-glioma activity by inducing ROS, and subsequently leads to autophagy and pyroptosis, highlighting its clinical potentials as a natural nutrient against glioblastoma.

摘要

胶质母细胞瘤是最常见且致命的颅内恶性肿瘤之一,目前仍缺乏理想的治疗方法。山奈酚是多种可食用植物中的一种主要营养成分,已显示出治疗胶质母细胞瘤的潜力。然而,山奈酚的具体抗胶质瘤机制尚待研究。在此,我们旨在探讨山奈酚抗胶质瘤活性的潜在机制。我们的结果表明,山奈酚可抑制胶质瘤细胞增殖并抑制肿瘤生长。此外,山奈酚可增加胶质瘤细胞中的活性氧(ROS)水平并降低线粒体膜电位。高水平的ROS诱导自噬,最终触发胶质瘤细胞的焦亡。有趣的是,当我们使用3-甲基腺嘌呤(3-MA)抑制自噬时,我们发现GSDME的裂解形式也减少了,这表明山奈酚通过调节胶质瘤细胞中的自噬来诱导焦亡。总之,本研究表明山奈酚通过诱导ROS具有良好的抗胶质瘤活性,随后导致自噬和焦亡,突出了其作为一种天然营养物质对抗胶质母细胞瘤的临床潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7508/7758214/b29f8be40054/fbioe-08-614419-g0001.jpg

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