Document Type

Journal Article

Department/Unit

Department of Chemistry

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

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.

Publication Year

2016

Journal Title

Free Radical Biology and Medicine

Volume number

92

Publisher

Elsevier

First Page (page number)

61

Last Page (page number)

77

Referreed

1

DOI

10.1016/j.freeradbiomed.2016.01.014

ISSN (print)

08915849

Link to Publisher’s Edition

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

Keywords

Apoptosis, Necroptosis, Cancer, MAM, ROS, NO

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