Acivicin induces apoptosis independently of gamma-glutamyltranspeptidase activity

Inhibition of cellular gamma -glutamyltranspeptidase (GGT) enzyme activity by its specific inhibitor acivicin is frequently used in studies aimed at d emonstrating the physiological role of this enzyme. However, because acivic in is a glutamine antagonist, it also inhibits many other glutamine-depende nt enzymes involved in purine and pyrimidine biosynthesis. The objective of the present work is to determine whether acivicin exhibits apoptotic prope rties and the significance of GGT activity level in the response to acivici n treatment. We compared acivicin (0-150 muM) effect on V79 cell lines expr essing or not expressing human GGT. Apoptosis was assayed by annexin-V stai ning, cell cycle analysis, and caspase activation using flow cytometry. We found that acivicin causes a dose- and time-dependent apoptosis in the GGT- negative V79 cell line as well as in its GGT-positive counterpart line. Thi s is the evidence that acivicin induces apoptosis in V79 cell independently of their GGT activity level. (C) 2001 Academic Press.