SULFORAPHANE AND OXOMATE: INHIBITORS OF TPA INDUCED NITRIC OXIDE SYNTHASE (INOS), CYCLOOXYGENASE 2 (COX-2) AND OXIDATIVE STRESS IN MURINE MACROPHAGE AND SKIN MODELS

Abstract

Excessive production of nitric oxide and cyclooxygenase 2 (COX-2) are thought to be causative factors of cellular injury and cancer. Sulforaphane acts as a potent detoxification enzyme inducer. We tested sulforaphane and oxomate for inhibition of inducible nitric oxide synthase (iNOS) and COX-2 in cultured mouse macrophage cells. Western blot analysis of whole cell lysates revealed that sulforaphane mediated a dosedependent decrease of lipopolysaccharide (LPS)-stimulated iNOS and COX-2 expression. Application of oxomate to LPS-stimulated macrophage cells revealed dosedependent inhibition of iNOS expression while no inhibition of COX-2 was detected. In mouse skin models, we found 12-0-Tetradecanoyl-phorbol-13-acetate (TPA) promoted oxidative stress events~ including altered levels of the reduced glutathione (GSH), myeloperoxidase and superoxide dismutase, that correlate with cancer. Results show unaltered levels of GSH in mice pretreated with sulforaphane and oxomate. These findings suggest that sulforaphane and oxomate have the potential to serve as cancer chemopreventive agents.