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γ-GLUTAMYLTRANSFERASE MODULATES L-γ-GLUTAMYL-P-NITROANILIDE (GPNA) CYTOTOXICITY: THE POOR SPECIFICITY OF AN OLD INHIBITOR OF GLUTAMINE TRANSPORT
Vol 32, Issue 4S1, 2018
Abstract
Glutamine (Gln) plays a critical role in supporting cell growth and proliferation of different cancercell types. Several studies have focused on the sodium-dependent Gln transporter ASCT2 as a potentialtherapeutic target and different approaches, including its inhibition or silencing, are commonly used.L-γ-glutamyl-p-nitroanilide (GPNA) is a widely used ASCT2 inhibitor, even if several concerns about itsspecificity have recently emerged since GPNA has a limited selectivity for ASCT2, being able to inhibitmany other transporters for amino acids.. Moreover, it is rarely considered that GPNA is also a wellknownsubstrate of the enzyme gamma-glutamyltransferase (GGT). The aim of this study was thus toevaluate the effect of GPNA catabolism by GGT on its efficacy as an inhibitor of cell proliferation.
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Medical Genetics, University of Torino Medical School, Italy
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy