Nuclear Factor-κB modulates cellular glutathione and prevents oxidative stress in cancer cells.
The NF-κB is best known for its role in inflammation. Here we show that constitutive NF-κB activity in cancer cells promotes the biosynthesis of redox scavenger glutathione (GSH), which in turn confers resistance to oxidative stress. Inhibition of NF-κB significantly decreases GSH in several lines of human leukemia and prostate cancer cells possessing high or moderate NF-κB activities. Concomitantly, NF-κB inhibition by pharmacological and molecular means sensitizes "NF-κB positive" cancer cells to chemically-induced oxidative stress and death. We propose that inhibition of NF-κB can reduce intracellular GSH in "NF-κB-positive" cancers thereby improving the efficacy of oxidative stress-based anti-cancer therapy.
Meng
Qinghang
Q
Department of Environmental Health, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, United States.
Peng
Zhimin
Z
Chen
Liang
L
Si
Jutong
J
Dong
Zhongyun
Z
Xia
Ying
Y
D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D018384:Oxidative Stress; D010087:Oxides / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
D001152:Arsenicals; D016328:NF-kappa B; D010087:Oxides; D005978:Glutathione; D000077237:Arsenic Trioxide
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