Apoptosis in human lymphoblastoid cells induced by acivicin, a specific gamma-glutamyltransferase inhibitor.
We examined the effects of acivicin, a specific inhibitor of the ectoenzyme gamma-glutamyltransferase (gamma-GT), on gamma-GT activity and apoptosis in 2 human T-lymphoblastoid CEM cell lines, CCRF and VBL-100. In both cell lines, acivicin was found to cause morphological and biochemical changes of apoptosis in a dose-dependent manner. There was a close correlation between inhibition of gamma-GT activity and the emergence of apoptotic cells. However, VBL-100 cells had a 50% higher gamma-GT basal activity than CCRF-CEM cells, their enzyme activity was more inhibited, and, they had a greater apoptotic response to acivicin. The gamma-GT-specific activity in apoptotic/dead cells was also almost totally inhibited, while that of cells that remained alive after 5 days of acivicin treatment was not. These findings confirm that gamma-GT is implicated in the process of apoptosis of CEM cells.
Graber
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Laboratorio di Patologia Cellulare, Istituto Cantonale di Patologia, Locarno, Switzerland.
Losa
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GA
D017209:Apoptosis / Q000187:drug effects*; D006801:Humans; D016130:Immunophenotyping; D007555:Isoxazoles / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D007555:Isoxazoles; D005723:gamma-Glutamyltransferase; C006303:acivicin