Description
Asparaginase is an enzyme that catalyzes the hydrolysis of asparagine to aspartate and ammonia, depleting asparagine levels and inhibiting cell growth; it is commonly used as an anticancer chemotherapeutic and anti-angiogenic compound in the treatment of leukemia. Asparaginase inhibits proliferation of acute myelogenous leukemia (AML) cells, inducing apoptosis mediated by apoptosis-inducing factor (AIF). Asparaginase decreases β1 integrin binding and phosphorylation of FAK, inducing autophagy; this decreases microvascular endothelial cell tube formation and inhibits invasion of ovarian cancer cells. In clinical settings, asparaginase may induce thrombotic effect, as administration often results in depletion of anti-thrombin, and it may also increase serum triglycerides.
References
He Y, Li B, Zhang H, et al. L-asparaginase induces in AML U937 cells apoptosis via an AIF-mediated mechanism. Front Biosci (Landmark Ed). 2014 Jan 1;19:515-27. PMID: 24389199.
Yu M, Henning R, Walker A, et al. L-asparaginase inhibits invasive and angiogenic activity and induces autophagy in ovarian cancer. J Cell Mol Med. 2012 Oct;16(10):2369-78. PMID: 22333033.
Nomme J, Su Y, Konrad M, et al. Structures of apo and product-bound human L-asparaginase: insights into the mechanism of autoproteolysis and substrate hydrolysis. Biochemistry. 2012 Aug 28;51(34):6816-26. PMID: 22861376.
Mitchell L, Andrew M, Hanna K, et al. Trend to efficacy and safety using antithrombin concentrate in prevention of thrombosis in children receiving l-asparaginase for acute lymphoblastic leukemia. Results of the PAARKA study. Thromb Haemost. 2003 Aug;90(2):235-44. PMID: 12888870.
Cremer P, Lakomek M, Beck W, et al. The effect of L-asparaginase on lipid metabolism during induction chemotherapy of childhood lymphoblastic leukaemia. Eur J Pediatr. 1988 Jan;147(1):64-7. PMID: 3422190.
