Abstract 3460: Reactive oxygen species generated by cadmium play a role in the upregulation of aldo-keto reductase 1C3 in RPMI 2630 nasal carcinoma cells

Abstract

Abstract Cadmium (Cd) is a carcinogenic metal which induces oxidative stress through the generation of reactive oxygen species (ROS). Therefore, the ability of cells to up-regulate their antioxidant enzymes is fundamental in the protection of cells and tissues from oxidative damage. In probing the possible survival mechanism of cancer cells to Cd-induced oxidative stress, we examined the ability of Cd to regulate the level of aldo-keto reductase 1C3 (AKR1C3), which has an anti-oxidative role that catalyzes the reductive detoxification of reactive aldehydes and ketones. Exposure of cells to Cd induced a dose- and time-dependent increase in the AKR1C3 expression in the RPMI 2640 nasal septum carcinoma cells, and this up-regulation was blocked by the free radical scavenger N-acetylcysteine (NAC). Additionally, we confirmed that Cd triggered a rapid increase in the intracellular ROS levels, and this increase was inhibited by pretreatment with NAC, which suggests that the up-regulation of AKR1C3 expression involves ROS signaling. Furthermore, pretreatment of cells with LY294002, a pharmacologic inhibitor of phosphatidylinositol-3-kinase (PI3K), suppressed the Cd-augmented AKR1C3 expression; however, inhibition of PKC or MEK1/2 signaling with Go6976 or PD98059, respectively, did not alter Cd-induced AKR1C3 expression. Collectively, these data suggest that Cd can modulate the expression of the AKR1C3 by activation of PI3K via the generation of ROS in RPMI2640 cells, which would contribute to adaptive response to oxidative stress. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3460.