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2-Methoxy-6-acetyl-7-methyljuglone (MAM), a natural naphthoquinone, induces NO-dependent apoptosis and necroptosis by H2O2-dependent JNK activation in cancer cells
Sun W.2; Bao J.2; Lin W.2; Gao H.2; Zhao W.2; Zhang Q.2; Leung C.-H.2; Ma D.-L.1; Lu J.2; Chen X.2
2016-03-01
Source PublicationFree Radical Biology and Medicine
ISSN18734596 08915849
Volume92Pages:61-77
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 (HO) 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 HO-dependent JNK activation in cancer cells. GSH depletion might play an initial role in MAM-induced cytotoxicity.

KeywordApoptosis Cancer Mam Necroptosis No Ros
DOI10.1016/j.freeradbiomed.2016.01.014
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS SubjectBiochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS IDWOS:000370645400006
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Cited Times [WOS]:25   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Hong Kong Baptist University
2.University of Macau
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Sun W.,Bao J.,Lin W.,et al. 2-Methoxy-6-acetyl-7-methyljuglone (MAM), a natural naphthoquinone, induces NO-dependent apoptosis and necroptosis by H2O2-dependent JNK activation in cancer cells[J]. Free Radical Biology and Medicine,2016,92:61-77.
APA Sun W..,Bao J..,Lin W..,Gao H..,Zhao W..,...&Chen X..(2016).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 and Medicine,92,61-77.
MLA Sun W.,et al."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 and Medicine 92(2016):61-77.
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