title: Acivicin induces apoptosis independently of gamma-glutamyltranspeptidase activity.
abstract: Inhibition of cellular gamma-glutamyltranspeptidase (GGT) enzyme activity by its specific inhibitor acivicin is frequently used in studies aimed at demonstrating the physiological role of this enzyme. However, because acivicin is a glutamine antagonist, it also inhibits many other glutamine-dependent enzymes involved in purine and pyrimidine biosynthesis. The objective of the present work is to determine whether acivicin exhibits apoptotic properties and the significance of GGT activity level in the response to acivicin treatment. We compared acivicin (0-150 microM) effect on V79 cell lines expressing or not expressing human GGT. Apoptosis was assayed by annexin-V staining, 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. This is the evidence that acivicin induces apoptosis in V79 cell independently of their GGT activity level.
authors.affiliation: Thiols et Fonctions Cellulaires, Faculty of Pharmacy, Laboratoire de Biochimie, 30, rue Lionnois, Nancy, 54000, France.
authors.forename: H
authors.initials: H
authors.lastname: Aberkane
authors.forename: P
authors.initials: P
authors.lastname: Frank
authors.forename: M M
authors.initials: MM
authors.lastname: Galteau
authors.forename: M
authors.initials: M
authors.lastname: Wellman
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000096:biosynthesis; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D004247:DNA; D005723:gamma-Glutamyltransferase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; C006303:acivicin