Pendulone induces apoptosis via the ROS-mediated ER-stress pathway in human non-small cell lung cancer cells

Wen Chien Cheng, Ya Wen, Yen Shuo Chiu, Chia Hao Chou, Chen Jen Lim, Sheng Hao Lin, Jia Ming Chang, Chi Chien Lin

研究成果: 雜誌貢獻文章同行評審

摘要

Purpose: Pendulone, an isoflavone compound, is known to act against human cancer cells. However, its role in human non-small cell lung cancer (NSCLC) and the exact molecular mechanisms of action have never been reported. Methods: We investigated the effects of pendulone on cell proliferation and apoptosis in human NSCLC H1299 cells. Cell viability was examined using the methyl-thiazol-diphenyl-tetrazolium (MTT) assay. Flow cytometry was employed to evaluate apoptotic indices such as the cell cycle, mitochondrial membrane potential, cytochrome c release, caspase activity, and death receptor expression. The expression of proteins related to the cell cycle and apoptosis were analyzed by Western blot analysis. Results: Pendulone significantly decreased H1299 cell viability by inducing endoplasmic reticulum (ER) stress through the accumulation of reactive oxygen species (ROS). Pendulone induced the expression of ER stress-associated proteins, such as ATF4 and CHOP, which promoted the expression of death receptors. Activation of caspase 8 induced extrinsic pathway apoptosis. Pendulone also caused the loss of mitochondrial membrane potential, inhibited the anti-apoptotic proteins BCL-2 and activated the pro-apoptotic protein BAX, which promoted the release of cytochrome c to activate caspase 9. Antioxidant N-acetylcysteine (NAC), with its ROS-suppressive property, reversed pendulone-induced ER stress and cell apoptosis. Conclusion: Our findings provide evidence that pendulone induces apoptosis by inducing ER stress through ROS accumulation and mitochondrial dysfunction in NSCLC cell lines.

原文英語
文章編號105346
期刊Toxicology in Vitro
81
DOIs
出版狀態已發佈 - 6月 2022

ASJC Scopus subject areas

  • 毒理學

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