Document Type

Journal Article

Title

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

Department/Unit

Department of Chemistry

Language

English

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.

Keywords

Apoptosis, Necroptosis, Cancer, MAM, ROS, NO

Publication Date

3-31-2016

Source Publication Title

Free Radical Biology and Medicine

Volume

92

Start Page

61

End Page

77

Publisher

Elsevier

Peer Reviewed

1

DOI

10.1016/j.freeradbiomed.2016.01.014

Link to Publisher's Edition

http://dx.doi.org/10.1016/j.freeradbiomed.2016.01.014

ISSN (print)

08915849

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