Butin decreases oxidative stress-induced 8-hydroxy-2′-deoxyguanosine levels via activation of oxoguanine glycosylase 1

Abstract

In response to oxidative DNA base damage, oxoguanine glycosylase 1 (OGG1), in a base-excision repair (BER) pathway in mammals, plays a vital role in the repair of 8-hydroxy-2′-deoxyguanosine (8-OHdG), which is a reliable marker of reactive oxygen species (ROS)-induced DNA base modification and contributes to the pathologic process of cancer. Recently, we have shown that butin (7,3′,4′-trihydroxydihydroflavone) protects cells against hydrogen peroxide (H 2O 2)-induced damage of cellular components including DNA. In the present study, we examined the possible protective effect of butin on oxidative stress-induced DNA base modification, especially 8-OHdG. Hydrogen peroxide significantly increased the level of 8-OHdG, which was detected by 8-OHdG ELISA and confocal microscopy, but butin decreased this level. Suppression of 8-OHdG formation by butin was related to the enhanced mRNA and protein expression of OGG1, which was detected by RT-PCR and Western blot analysis. Butin also increased the transcriptional activity of OGG1, which was suppressed by H 2O 2 treatment; this transcriptional activity was detected by OGG1 promoter luciferase assay. Butin enhanced the expression of phosphorylated Akt (active form of Akt), a regulator of OGG1, which was decreased by H 2O 2 treatment. A PI3K-specific inhibitor, LY294002, abolished the phosphorylated Akt and OGG1 expressions induced by butin, suggesting that OGG1 induction by butin involves the PI3K/Akt pathway. © 2009 Elsevier Ireland Ltd. All rights reserved.