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 concentrationand
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.
Sulfur Mustard Analog Mechlorethamine (Bis(2-chloroethyl)methylamine) Modulates Cell Cycle Progression via the DNA Damage Response in Human Lung Epithelial A549 Cells