Azaserine is a glutamine antagonist [1]. Azaserine inhibits glutamine amidotransferase, interfering with the production of purine nucleotides and thereby inhibiting DNA and RNA synthesis [2]. Azaserine inhibits the hexamine biosynthesis pathway, reducing the production of UDP-N-acetylglucosamine and protein O-glycosylation, thereby affecting cellular glucose metabolism and protein post-translational modification [3]. Azaserine is primarily used to treat pancreatic tumors [4].
In R28 cells, Azaserine (0.1μM; 24h) blocks the entry of glucose into the hexosamine biosynthesis pathway (HBP), thereby reversing the inhibition of high glucose on the anti-apoptotic effect of insulin [5]. In Raji cells, Azaserine (5μM; 24h) inhibits cell growth [6].
References:
[1]. Livingston R B, Venditti J M, Cooney D A, et al. Glutamine antagonists in chemotherapy[J]. Advances in Pharmacology, 1971, 8: 57-120.
[2]. SARTORELLI A C, BOOTH B A. Inhibition of the synthesis of thymine nucleotides by azaserine[J]. Molecular Pharmacology, 1967, 3(1): 71-80.
[3]. Rajapakse A G, Ming X F, Carvas J M, et al. The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects[J]. American Journal of Physiology-Heart and Circulatory Physiology, 2009, 296(3): H815-H822.
[4]. Longnecker D S, Curphey T J. Adenocarcinoma of the pancreas in azaserine-treated rats[J]. Cancer research, 1975, 35(8): 2249-2257.
[5]. Nakamura M, Barber A J, Antonetti D A, et al. Excessive hexosamines block the neuroprotective effect of insulin and induce apoptosis in retinal neurons[J]. Journal of Biological Chemistry, 2001, 276(47): 43748-43755.
[6]. O'Driscoll M, Macpherson P, Xu Y Z, et al. The cytotoxicity of DNA carboxymethylation and methylation by the model carboxymethylating agent azaserine in human cells[J]. Carcinogenesis, 1999, 20(9): 1855-1862.