3′-Hydroxy-4′-methoxy-β-methyl-β-nitrostyrene inhibits tumor growth through ROS generation and GSH depletion in lung cancer cells

Chun Hao Tsai, Pei Wen Hsieh, Yi Chen Lee, Chie Hong Wang, Wen Chin Chiu, Chun Wun Lu, Yen Yun Wang, Stephen Chu Sung Hu, Tain Lu Cheng, Shyng Shiou F. Yuan*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

10 引文 斯高帕斯(Scopus)

摘要

Aims Members of the β-nitrostyrene family are known to suppress tumor growth, with the underlying mechanisms of β-nitrostyrene remain mostly unclear. Herein, we synthesized a β-nitrostyrene derivative, 3′-hydroxy-4′-methoxy-β-methyl-β-nitrostyrene (CYT-Rx20), and explored its anticancer activities in human lung cancer cells in vitro and in vivo. Main methods Cell viability was measured by XTT assay. Apoptosis was detected by Annexin V/PI staining. Caspase activation was determined by western blotting. ROS (reactive oxygen species), MMP (mitochondrial membrane potential) and mitochondrial mass were determined by flow cytometry. GSH level was detected by ELISA assay. Key findings In this study, we found that CYT-Rx20 significantly reduced cell viability, accompanied by G2/M arrest in lung cancer cells. Increased protein levels of cleaved-caspase families indicated apoptotic cell death upon CYT-Rx20 treatment. Furthermore, increased level of intracellular reactive oxygen species (ROS), loss of mitochondrial membrane potential (ΔΨm), glutathione (GSH) depletion and inhibition of GSH reductase were observed after CYT-Rx20 treatment. The effects of CYT-Rx20 on cell viability and the loss of ΔΨm were significantly reversed when cells were pretreated with thiol antioxidants NAC, GSH, or 2-ME. Finally, xenograft animal study demonstrated that CYT-Rx20 significantly suppressed lung tumor growth in vivo. Significance Our data demonstrated that CYT-Rx20 triggered apoptotic cell death in lung cancer cells and suppressed lung tumor growth through GSH depletion, suggesting that CYT-Rx20 may have the potential to be further developed as an anticancer compound for treating lung cancer.

原文英語
頁(從 - 到)19-26
頁數8
期刊Life Sciences
172
DOIs
出版狀態已出版 - 01 03 2017

文獻附註

Publisher Copyright:
© 2016 Elsevier Inc.

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