Catalase as a Potential Biomarker of Pharmacological Ascorbate Cancer Therapy

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 H 2 O 2 , 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 H 2 O 2 . The principal enzymes responsible for the elimination of H 2 O 2 are catalase, glutathione peroxidase (GPx) and peroxiredoxins (Prx). Among these, catalase is the principal enzyme that involved in the detoxification of H 2 O 2 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.