Antitumor potential of glutaminase- and urease-free L-asparaginase from Antarctic fungus Mortierella turficola.

L-Asparaginase (L-ASNase) is a chemotherapy drug that has been used as a therapy for the treatment of some types of cancer, including leukemia and lymphoma. Its action involves inhibiting the growth of tumor cells by reducing the availability of asparagine in the body. L-ASNase is an enzyme produced by microorganisms; however, they have adverse effects, which may be related to the activities of glutaminase and urease. Bioprospecting in cold environments, such as the Antarctic continent, may be a promising alternative in the search for enzymes with differentiated properties. For these reasons, the present study evaluated the production of glutaminase- and urease-free L-asparaginase by fungi isolated from soil and wood collected on two islands of the South Shetland Archipelago, Antarctica. A total of 39 filamentous fungi were recovered. Mortierella turficola FM2.1, isolated from wood, produced only L-asparaginase in a solid culture medium assay, showing an enzymatic index of 2.83. The effects of enzymatic extracts on HBMEC, MRC-5, and MIAPaCa-2 cell lines were investigated. MTT assay showed IC lower than that of the control, especially in the carcinogenic MIAPaCa-2 cell line. Fluorescence analysis of MIA PaCa-2 showed deformations in the cytoskeleton and nucleus of cells treated with enzymatic extracts up to 50%, in addition to a reduction in cell quantity. These results suggest that L-ASNase produced by the FM2.1 strain may have potential application in the treatment of pancreatic cancer. However, cytotoxic action has been observed in non-tumor cells. Future studies on the characterization of L-ASNase from enzymatic extracts for biotechnological applications should be conducted, aiming for trials with fewer side effects.