Cepharanthine Regulates Autophagy via Activating the p38 Signaling Pathway in Lung Adenocarcinoma Cells.

Gang Li, Kesen Qiao, Xiaodan Xu, Chao Wang

Anti-cancer agents in medicinal chemistry 2022

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Cepharanthine (CEP) is an alkaloid extracted from Stephania cepharantha Hayata. This compound has been reported as a promising anti-tumor drug, although its potential molecular mechanism is not fully understood. Here, we studied the anti-tumor effect of CEP on human lung cancer cells and evaluated its molecular mechanism. The A549 cells were treated with CEP, the cell viability was measured by 3-(4, 5-dimethylthiazolyl-2)-2, 5- diphenyltetrazolium bromide (MTT) assay, and formation of autophagosome was observed by acridine orange staining under a fluorescence microscope. The cell migration and invasion were determined by wound healing and transwell assay. The protein levels of autophagy-associated molecules, light chain 3 (LC3)p38 and phospho-p38 in A549 cells, were determined by western blot analysis. The results showed that CEP inhibited cell proliferation, migration and invasion in A549 cells. Moreover, we found that CEP resulted in significant increases in levels of the autophagy marker protein LC3 in A549 cells. The number of intracellular acid dye follicular bright red fluorescence in A549 cells was significantly increased after CEP treatment. At the molecular levels, CEP markedly increased the phosphorylation of p38 in A549 cells. The knockdown of p38 expression by siRNA-p38 impaired the autophagy-regulating effect of CEP. Our results indicated that CEPregulated autophagy was an anti-tumor effect and not a protective response to CEP. Taken together, these results demonstrated that CEP regulated autophagy by activating the p38 signaling pathway, which could be provided a potential application for preventing lung cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Citation

Gang Li, Kesen Qiao, Xiaodan Xu, Chao Wang. Cepharanthine Regulates Autophagy via Activating the p38 Signaling Pathway in Lung Adenocarcinoma Cells. Anti-cancer agents in medicinal chemistry. 2022;22(8):1523-1529