Fu J Y, Jiang C X, Wu M Y, Mei R Y, Yang A F, Tao H P, Chen X J, Zhang J, Huang L, Zhao X F
Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China.
Department of Physiology, Research Center of Neuroscience, College of Basic Medical Science, Chongqing Medical University, Chongqing, China.
Front Pharmacol. 2021 Apr 30;12:664003. doi: 10.3389/fphar.2021.664003. eCollection 2021.
Theabrownin (TB), a natural compound present in the fresh leaves of green tea, is a potential antitumor agent. However, so far whether and how TB affects glioma is unclear. In this study, we investigated the effect of TB on astroglioma and oligodendroglioma cells. Surprisingly, TB significantly reduced the viabilities of HOG and U251 cells in a dose-dependent manner, which was accompanied by the upregulation of active-Casp-3, Bax, and PTEN; meanwhile, the antiapoptotic gene Bcl-2 was downregulated. In addition, TB treatment induced cell cycle arrest at the G1 and G2/M phases in HOG and U251 cells, respectively. TB treatment caused the downregulating of c-myc, cyclin D, CDK2, and CDK4 and upregulating of p21 and p27 in the HOG cell, while TB increased P53, p21, and p27 levels and decreased the levels of cell cycle regulator proteins such as CDK and cyclin A/B in the U251 cells. Therefore, the c-myc- and P53-related mechanisms were proposed for cell cycle arrest in these two glioma cell lines, respectively. Overall, our findings indicated that TB could be a novel candidate drug for the treatment of gliomas.
茶褐素（TB）是绿茶鲜叶中存在的一种天然化合物，是一种潜在的抗肿瘤药物。然而，迄今为止，TB是否以及如何影响神经胶质瘤尚不清楚。在本研究中，我们研究了TB对星形胶质瘤和少突胶质细胞瘤细胞的影响。令人惊讶的是，TB以剂量依赖性方式显著降低了HOG和U251细胞的活力，同时伴随着活性Casp-3、Bax和PTEN的上调；与此同时，抗凋亡基因Bcl-2被下调。此外，TB处理分别诱导HOG和U251细胞在G1期和G2/M期发生细胞周期阻滞。TB处理导致HOG细胞中c-myc、细胞周期蛋白D、细胞周期蛋白依赖性激酶2（CDK2）和细胞周期蛋白依赖性激酶4（CDK4）下调，p21和p27上调，而TB增加U251细胞中P53、p21和p27的水平，并降低细胞周期调节蛋白如CDK和细胞周期蛋白A/B的水平。因此，分别提出了c-myc和P53相关机制导致这两种神经胶质瘤细胞系的细胞周期阻滞。总体而言，我们的研究结果表明，TB可能是一种治疗神经胶质瘤的新型候选药物。
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