none8Tiazofurin, an anticancer drug which inhibits IMP dehydrogenase, decreases cellular GTP concentration,
induces differentiation and down-regulates ras and myc oncogene expression, caused apoptosis of K562
cells in a time- and dose-dependent fashion. Apoptotic cells were detected by (1) flow cytometry, (2) electron
microscopy, and (3) fluorescence in situ nick translation and confocal microscopy, while the DNA ladder was
not detectable. The induced apoptosis was abrogated by guanosine which replenishes GTP pools through the
guanosine salvage pathways, while it was enhanced by hypoxanthine, a competitive inhibitor of GPRT. The
tiazofurin-mediated apoptosis may therefore be linked with the decrease of GTP and the consequent
impairment of specific signal transduction pathways. Tiazofurin induced apoptosis also in lymphoblastic
MOLT-4 cells, suggesting that this action is not confined to cells of the myeloid lineage, where the
differentiating effects of the drug are more pronounced.openVITALE M; ZAMAI L; FALCIERI E; ZAULI G; GOBBI P.; SANTI S; CINTI C; WEBER GVitale, M; Zamai, Loris; Falcieri, Elisabetta; Zauli, G; Gobbi, Pietro; Santi, S; Cinti, C; Weber, G
