Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer
Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer
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DOI：
10.1159/000481698
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Zhang, Aili
中科院分区：
文献类型：
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作者：
Fan, Bo;Zhang, Xiaoyu;Zhang, Aili
背景/目的：粉防己碱和防己诺林碱（Fcn）是从粉防己中发现的两种天然产物。汉防己甲素是一种已知的抗膀胱癌化合物，但FCN对膀胱癌的影响以前一直不清楚。本研究主要探讨Fcn对膀胱癌的抗肿瘤作用。方法和结果：我们在体外用Fcn处理T24和5637膀胱癌细胞系。我们观察到，Fcn抑制膀胱癌细胞的活力在浓度依赖性的方式。增殖标志物PCNA表达下调。Fcn处理诱导膀胱癌细胞凋亡和自噬，如通过增加caspase-3的切割，上调LC 3-II/LC 3-I比率和下调p62水平所示。用3-MA（3-Methyladenine）阻断自噬增强Fcn诱导的细胞凋亡，表明Fcn诱导的自噬是适应性的。此外，我们观察到Fcn处理抑制mTOR并降低细胞内ATP水平。外源性丙酮酸甲酯（MP）的加入，以补偿代谢底物减轻Fcn诱导的细胞凋亡和自噬。结论：我们的数据表明，Fcn引起的能量产生障碍，导致细胞凋亡和适应性自噬在膀胱癌。这些结果表明，Fcn可能是一个潜在的候选用于预防和治疗膀胱癌。(C)2017作者（s）由S. Karger AG，巴塞尔
Background/Aims: Tetrandrine and Fangchinoline (Fcn) are two natural products that are found in Stephania tetrandra. Tetrandrine is a known anti-bladder cancer compound, but the effects of Fcn on bladder cancer have been previously unclear. In the present study, we focused on the anti-tumor effects of Fcn on bladder cancer. Methods and Results: We treated T24 and 5637 bladder cancer cell lines with Fcn in vitro. We observed that Fcn inhibited the viability of bladder cancer cells in a concentration-dependent manner. The expression of PCNA, a biomarker of proliferation, was down-regulated. Fcn treatment induced both apoptosis and autophagy in bladder cancer cells, as shown by the increased cleavage of caspase-3, an up-regulated LC3-II/LC3-I ratio and the down-regulated p62 level. Blocking autophagy with 3-MA (3-Methyladenine) enhanced Fcn-induced apoptosis, indicating that Fcn-induced autophagy was adaptive. Additionally, we observed that Fcn treatment inhibited mTOR and reduced the intracellular ATP levels. The exogenous addition of methyl pyruvate (MP) to compensate metabolic substrates alleviated Fcn-induced apoptosis and autophagy. Conclusions: Our data indicated that Fcn caused an impairment in energy generation, which led to apoptosis and adaptive autophagy in bladder cancer. These results demonstrated that Fcn may be a potential candidate for use in the prevention and treatment of bladder cancer. (C) 2017 The Author(s) Published by S. Karger AG, Basel