Abstract 2068: Opposite effects of arsenic trioxide on the Nrf2 pathway in oral squamous cell carcinoma in vitro and in vivo

Abstract

Abstract Nuclear factor erythroid derived like 2 (Nrf2) is a critical transcriptional factor in mediating cellular defense mechanisms against oxidative stress or electrophiles. Arsenic has been reported to induce malignant transformation of human cells through Nrf2-dependent signaling pathway. However, arsenic is also a promising cancer therapeutic drug for solid tumors, including oral squamous cell carcinoma (OSCC). It is still unclear how Nrf2 may mediate cellular response of OSCC cells when treated with arsenic. In order to fully understand the impact of Nrf2 signaling in human OSCC, we examined expression of Nrf2 and Nrf2-regulated genes in arsenic trioxide (ATO) treated OSCC cells in vitro and in ATO-treated OSCC xenografts. ATO exerted its anti-tumor effects on both cultured OSCC cells and OSCC xenografts by inhibiting cell growth, suppressing angiogenesis and inducing apoptosis. ATO activated a silent Nrf2 pathway in cultured OSCC cells as shown by induction of Nrf2 and Nrf2-regulated genes, NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), in a dose-dependent manner. On the contrary, Nrf2 pathway became active in OSCC xenograft tumors, and ATO treatment down-regulated expression of Nrf2 and Nrf2-regulated genes. Our study clearly demonstrated opposite effects of ATO on Nrf2 pathway in OSCC in vitro and in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2068. doi:1538-7445.AM2012-2068