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首页> 外文期刊>Cellular Physiology and Biochemistry >Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer
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Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer

机译：芳基胆碱诱导膀胱癌的凋亡，自噬和能量受损。

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>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.
机译：> 背景/目标： 粉防己碱和芳基胆碱（Fcn）是在 Stephania tetrandra 中发现的两种天然产物。粉防己碱是一种已知的抗膀胱癌化合物，但以前尚不清楚Fcn对膀胱癌的作用。在本研究中，我们集中于Fcn对膀胱癌的抗肿瘤作用。 方法和结果： 我们在体外用Fcn 处理了T24和5637膀胱癌细胞系。我们观察到Fcn以浓度依赖的方式抑制膀胱癌细胞的活力。 PCNA，增殖的生物标志物的表达被下调。 Fcn处理可诱导膀胱癌细胞凋亡和自噬，如caspase-3裂解增加，LC3-II / LC3-I比例上调和p62水平下调所示。用3-MA（3-甲基腺嘌呤）阻断自噬增强了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处理可抑制mTOR并降低细胞内ATP水平。丙酮酸（MP）的外源性添加以补偿代谢底物减轻了Fcn诱导的细胞凋亡和自噬。 结论： 我们的数据表明Fcn导致能量生成受损，从而导致膀胱癌的凋亡和适应性自噬。这些结果表明，Fcn可能是用于预防和治疗膀胱癌的潜在候选药物。

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