Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer.
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.
['Fan|Bo|B|', 'Zhang|Xiaoyu|X|', 'Ma|Yongliang|Y|', 'Zhang|Aili|A|']
D000225:Adenine D000255:Adenosine Triphosphate D000970:Antineoplastic Agents D017209:Apoptosis D001343:Autophagy D044182:Benzylisoquinolines D053148:Caspase 3 D045744:Cell Line, Tumor D002470:Cell Survival D006801:Humans D008869:Microtubule-Associated Proteins D018809:Proliferating Cell Nuclear Antigen D011773:Pyruvates D016601:RNA-Binding Proteins D031609:Stephania tetrandra D058570:TOR Serine-Threonine Kinases D001749:Urinary Bladder Neoplasms
Fangchinoline Apoptosis Autophagy Bladder cancer Proliferation