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2-Methoxy-6-acetyl-7-methyljuglone (MAM), a natural naphthoquinone, induces NO-dependent apoptosis and necroptosis by H 2 O 2 -dependent JNK activation in cancer cells
- Source :
- Free Radical Biology and Medicine. 92:61-77
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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.
- Subjects :
- 0301 basic medicine
Programmed cell death
Necroptosis
Melanoma, Experimental
Nitric Oxide Synthase Type II
Apoptosis
Biology
Nitric Oxide
medicine.disease_cause
Biochemistry
Nitric oxide
Mice
Necrosis
03 medical and health sciences
chemistry.chemical_compound
Cell Line, Tumor
Physiology (medical)
medicine
Animals
Humans
Intrinsic apoptosis
JNK Mitogen-Activated Protein Kinases
Hydrogen Peroxide
Glutathione
Cell biology
Nitric oxide synthase
Oxidative Stress
030104 developmental biology
chemistry
Cancer cell
MCF-7 Cells
biology.protein
Reactive Oxygen Species
Oxidative stress
Naphthoquinones
Subjects
Details
- ISSN :
- 08915849
- Volume :
- 92
- Database :
- OpenAIRE
- Journal :
- Free Radical Biology and Medicine
- Accession number :
- edsair.doi.dedup.....01b0bb6ed5723694a8b993b455ca4603