Growth inhibitory and proapoptotic effects of l‐asparaginase from Fusarium culmorum ASP‐87 on human leukemia cells (Jurkat)

Abstract

The objective of this study was to evaluate the anticancer properties of l-asparaginase purified from fungal isolate Fusarium culmorum ASP-87 against human T-cell leukemia cell line (Jurkat). The growth inhibitory and proapoptotic effects of purified l-asparaginase on Jurkat cell lines were investigated by determining its influence on cell viability, colony formation, DNA fragmentation, and cell cycle progression. The results revealed that purified l-asparaginase showed significant decrease in cell survival with IC value of 90 μg/mL (9 IU/mL). The enzyme inhibited colony formation and showed characteristic laddering pattern on agarose gel thereby confirming the induction of apoptosis. Further, cell cycle analysis revealed that the enzyme induced apoptotic cell death by arresting the growth of cells at G -M phase. However, the enzyme did not elicit any toxic effects on human erythrocytes. l-asparaginase purified from F. culmorum ASP-87 showed significant and selective cytotoxic and apoptotic effects on human T-cell leukemic cells in dose-dependent manner. Results of the study give leads for the anticancer effects of fungal l-asparaginase and its potential usefulness in the chemotherapy of leukemia.

Molecular Analysis of L-Asparaginases for Clarification of the Mechanism of Action and Optimization of Pharmacological Functions

“…The role of chemical modifications and protein engineering in improving the effectiveness of medicines is also discussed. Currently, as an alternative to bacterial L-ASNases with chemotherapeutic use, several type II bacterial enzymes are under consideration: Thermus thermophiles , Proteus vulgaris , Pseudomonas fluorescens , Serratia marcescens , Erwinia aroidea , Aspergillus terreus , Mycobacterium tuberculosis , Yersinia pseudotuberculosis , recombinant Saccharomyces cerevisiae , Halomonas elongata , Sarocladium strictum , Streptomyces rochei , Aspergillus terreus , Fusarium culmorum and Zymomonas mobilis [ 62 , 138 , 139 , 140 , 141 , 142 ]. They all have antiproliferative activities toward cancer cells.…”