Abstract 5099: Adiponectin inhibits oxidative stress in prostate cancer cells

Abstract INTRODUCTION AND OBJECTIVES: Emerging data suggest that obesity increases the risk of aggressive prostate cancer (PC) but the mechanisms underlying this relationship remain to be fully elucidated. Adiponectin, an adipocyte-specific hormone, circulates at relatively high levels in healthy human but its levels are reduced in obesity. Case control studies have documented an association between lower adiponectin blood levels and PC implying that obese individuals with low adiponectin levels are more susceptible in developing PC. In this study we examined the effect of adiponectin on the generation and reduction of oxidative stress (OS) in PC cells, a process that intimately relates to the initiation and development of PC. METHOD: As models we used two human PC cell lines (22rv1 and DU145) expressing the adiponectin receptors AdipoR1, AdipoR2 and T-cadherin. Cells were treated with increasing doses of human recombinant adiponectin (0-40μg/ml) and were subjected to the following tests: Quantification of cellular OS (NBT reduction assay), expression of catalase and MnSOD (Western blot analysis), comparison of transcript levels of NADPH oxidases (NOX) enzymes- a major source of reactive oxygen species in PC cells (RT-PCR) and determination of the global cellular anti-oxidative capacity and catalase activity (colorimetric assays). RESULT: Adiponectin significantly inhibited OS in both cell types in a dose dependent manner by inducing the expression of the two key anti-oxidative enzymes; catalase and MnSOD, leading to an increase in the anti-oxidative capacity of the cells. Treatment with adiponectin reduced Nox 2,4 mRNA expression in Du145 cells but increased it in 22RV1 cells. CONCLUSIONS: These results suggest a protective role for adiponectin against the initiation and development of PC, through OS inhibition. 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 5099.