Cell-cycle disruptions and apoptosis induced by the cyclophosphamide derivative mafosfamide.
The effect of the cyclophosphamide derivative mafosfamide (ASTA Z 7557) was investigated in vitro in HL60 leukemic cells. Mafosfamide, which rapidly generates 4-hydroxycyclophosphamide after aqueous dissolution, was employed at doses ranging from 0.1 to 10 micrograms/mL. In unsynchronized cells, mafosfamide exposure was associated with an S-phase accumulation, a suggestion of a G2-phase arrest and morphological and biochemical evidence of apoptosis. In cells that had been synchronized by the double thymidine block method, S-phase progression was considerably delayed in the presence of mafosfamide. The apoptosis that was evident in mafosfamide-treated cells 12 hours after release from the thymidine block was found to occur in the presence of S-phase and G2-phase cell-cycle arrests. Taken together, the current data suggest that mafosfamide may have potential synergism with other anticancer agents that elicit similar cell-cycle arrests as well as with chemotherapeutic drugs that activate the apoptotic cascade.
Davidoff
A N
AN
Department of Haematology, School of Pathology of the University of the Witwatersrand, South Africa.
Mendelow
B V
BV
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D016196:S Phase / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C048341:mafosfamide; D003520:Cyclophosphamide