2-Methoxy-6-acetyl-7-methyljuglone (MAM), a natural naphthoquinone, induces NO-dependent apoptosis and necroptosis by H2O2-dependent JNK activation in cancer cells

Free Radical Biology & Medicine
Wen SunXiuping Chen

Abstract

Redox signaling plays a fundamental role in maintaining cell physiological activities. A deregulation of this balance through oxidative stress or nitrosative stress has been implicated in cancer. Here, we reported that 2-methoxy-6-acetyl-7-methyl juglone (MAM), a natural naphthoquinone isolated from Polygonum cuspidatum Sieb. et Zucc, caused hydrogen peroxide (H2O2) dependent activation of JNK and induced the expression of inducible nitric oxide synthase (iNOS), thereby leading to nitric oxide (NO) generation in multiple cancer cells. Nitrosative stress induced necroptosis in A549 lung cancer cells, but resulted in caspase-dependent intrinsic apoptosis in B16-F10 melanoma and MCF7 breast cancer cells. In addition, a decrease in GSH/GSSG levels accompanied with increased ROS production was observed. Reversal of ROS generation and cell death in GSH pretreated cells indicated the involvement of GSH depletion in MAM mediated cytotoxicity. In summary, a natural product MAM induced NO-dependent multiple forms of cell death in cancer cells mediated by H2O2-dependent JNK activation in cancer cells. GSH depletion might play an initial role in MAM-induced cytotoxicity.

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Citations

Nov 19, 2018·Amino Acids·Mostafa A L Abdel-SalamElaine Maria de Souza-Fagundes
Sep 12, 2017·Annals of the New York Academy of Sciences·Renyikun YuanXiuping Chen
Jul 12, 2019·Phytotherapy Research : PTR·Onsurang WattanathamsanVarisa Pongrakhananon
Aug 8, 2019·Cancer Cell International·Carolina Escardó PereyraFloriano Paes Silva-Jr
Dec 16, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Heng-Long WangJer-Yiing Houng
Mar 20, 2021·Photodermatology, Photoimmunology & Photomedicine·Ziting TangShengbo Yang
Jul 24, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Jyoti SinghAbha Meena

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