Nuclear Factor-κB modulates cellular glutathione and prevents oxidative stress in cancer cells

Abstract

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.