DIETARY FLAVONOIDS REDUCE CARCINOGEN-INDUCED DNA DAMAGE IN BRONCHIAL EPITHELIAL CELLS IN VITRO

Abstract

The potential of selected flavonoids in reducing carcinogen-induced reactive oxygen species (ROS) and DNA damage through the activation of nuclear factor erythroid 2 p45 (NF-E2)-related factor (Nrf2)/antioxidant response element (ARE) pathway was studied in vitro. Dose-dependent effects of pre-incubated flavonoids on pro-carcinogen 4-[(acetoxymethyl)nitrosamino]-1-(3-pyridyl)-1-butanone (NNKAc)-induced ROS and DNA damage in human bronchial epithelial cells were studied in comparison to non-flavonoids. The most effective flavonoids were assessed for the activation of Nrf2/ARE pathway. Genistein, procyanidin B2 (PCB2), and quercetin significantly suppressed the NNKAc-induced ROS and DNA damage. PCB2 significantly upregulated the activation of Nrf2 and protein kinase B through phosphorylation. Genistein and PCB2 significantly upregulated the phospho-Nrf2 nuclear translocation and catalase activity. In summary, quercetin, genistein, and PCB2 reduced the NNKAc-induced ROS and DNA damage in concert with activation of Nrf2. Further studies are required to understand the role of dietary flavonoids on the regulation of Nrf2/ARE pathway in relation to carcinogenesis.