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2-methoxy-6-acetyl-7-methyljuglone (MAM) induces iNOS/NO-mediated DNA damage response through activation of MAPKs pathways
Niu Y.3; Yuan R.3; Gao H.3; Lu J.-J.3; Kong Q.1; Chen X.3
2018
Source PublicationAnti-Cancer Agents in Medicinal Chemistry
ISSN18755992 18715206
Volume18Issue:6Pages:903-913
Abstract

Background:There are inconsistent reports about the role of Nitric Oxide (NO) in cancer progression and prevention. Quinones demonstrate significant anti-cancer activities both in vitro and in vivo. Objective: We investigated the effect of 2-methoxy-6-acetyl-7-methyljuglone (MAM), a natural naphthoquinone isolated from Polygonum cuspidatum Sieb. et Zucc, on NO generation and its role in DNA damage in cancer cells. Methods: BEL-7402 and A549 cells were cultured and treated with MAM. The NO generation, DNA damage, and protein expression were determined. Results: MAM induced inducible nitric oxide synthase (iNOS)/NO-mediated DNA damage response through activation of MAPKs pathways. MAM induced DNA damage by activating ATM/Chk2. MAM increased iNOS expression, NO production, and MAPKs (JNK1/2, ERK1/2, and p38MAPK) phosphorylation in concentration-and time-dependent manners. Furthermore, iNOS inhibitor 1400W, iNOS siRNA, and NO scavenger hemoglobin (Hb) could significantly reverse MAM-induced DNA damage, ATM/Chk2 activation, NO production, and cell death. In addition, MAPKs inhibitors (SP600125, U0126, and SB203580) reversed MAM-induced cell death and ATM/Chk2 activation. MAM-induced cell death was partially reversed by 1400W and Hb but enhanced by L-arginine. Conclusion: These results suggested that MAM induced iNOS/NO activation and generation mediated by MAPKs pathways, which resulted in DNA damage.

KeywordAtm/chk2 Dna Damage Inos/no L-arginine Mam Mapks
DOI10.2174/1871520618666180411111950
URLView the original
Indexed BySCI
WOS Research AreaOncology ; Pharmacology & Pharmacy
WOS SubjectOncology ; Chemistry, Medicinal
WOS IDWOS:000450010700016
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Chinese Academy of Medical Sciences
2.Hebei Medical University
3.Universidade de Macau
Recommended Citation
GB/T 7714
Niu Y.,Yuan R.,Gao H.,et al. 2-methoxy-6-acetyl-7-methyljuglone (MAM) induces iNOS/NO-mediated DNA damage response through activation of MAPKs pathways[J]. Anti-Cancer Agents in Medicinal Chemistry,2018,18(6):903-913.
APA Niu Y.,Yuan R.,Gao H.,Lu J.-J.,Kong Q.,&Chen X..(2018).2-methoxy-6-acetyl-7-methyljuglone (MAM) induces iNOS/NO-mediated DNA damage response through activation of MAPKs pathways.Anti-Cancer Agents in Medicinal Chemistry,18(6),903-913.
MLA Niu Y.,et al."2-methoxy-6-acetyl-7-methyljuglone (MAM) induces iNOS/NO-mediated DNA damage response through activation of MAPKs pathways".Anti-Cancer Agents in Medicinal Chemistry 18.6(2018):903-913.
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