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

Wen Sun, Jiaolin Bao, Wei Lin, Hongwei Gao, Wenwen Zhao, Qingwen Zhang, Chung Hang Leung, Edmond Dik Lung MA, Jinjian Lu, Xiuping Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)61-77
Number of pages17
JournalFree Radical Biology and Medicine
Publication statusPublished - Mar 2016

Scopus Subject Areas

  • Biochemistry
  • Physiology (medical)

User-Defined Keywords

  • Apoptosis
  • Cancer
  • MAM
  • Necroptosis
  • NO
  • ROS


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