271 - Catalase as a Potential Biomarker of Pharmacological Ascorbate Cancer Therapy

Abstract

Pharmacological ascorbate (P-AscH–) has been shown to induce toxicity in a various cancer cell lines both in vitro and in vivo. P-AscH– can readily oxidize and deliver a high flux of H2O2, which can easily cross cell membrane and convert to more reactive species inside the cell. We hypothesize differential sensitivity of cells to P-AscH– is due to their ability to remove H2O2. The principal enzymes responsible for the elimination of H2O2 are catalase, glutathione peroxidase (GPx) and peroxiredoxins (Prx). Among these, catalase is the principal enzyme that involved in the detoxification of H2O2 at high concentration. In this study, we compared catalase levels and peroxide removal capacity in several pancreatic cancer cell lines MIA PaCa-2, AsPC-1, 403, 339 and Panc-1. Preliminary results indicated that MIA PaCa-2 cells had the lowest level of catalase and were most sensitive to P-AscH–, while Panc-1 had the highest level of catalase and were the least sensitive. In mice with pre-established xenograft pancreatic tumor, P-AscH– (4g/kg, i.p. twice daily) showed a greater inhibition of tumor growth for MIA PaCa-2 xenografts in comparison to Panc-1 xenografts. Furthermore, immunofluorescent staining of catalase in xenograft tumors also indicated that MIA PaCa-2 had lower level of catalase than Panc-1 in vivo. Taken together, catalase activity in tumors may predict which cancers will respond to P-AscH– therapy. Supported by VA Merit grant and NIH grants CA184051, CA137230, and CA169046.