C-myc expression is down-regulated in mafosfamide-treated HL-60 cells undergoing apoptosis.
The expression of the proto-oncogene c-myc has been strongly implicated in the regulation of apoptosis. Since we have previously shown apoptosis to occur in HL-60 leukemic cells exposed to the prodrug Mafosfamide (ASTA Z 7557), the present study was undertaken to examine the levels of c-myc mRNA transcripts in such cells. Mafosfamide, which is a cyclophosphamide derivative that rapidly generates 4-Hydroperoxycyclophosphamide after aqueous dissolution, was employed in doses ranging from 0.1 to 20 micrograms/ml. No changes in c-myc mRNA levels were evident after 1 hour of exposure to Mafosfamide. After 6 and 24 hours of Mafosfamide-exposure, however, there was a dose- and time-dependent decrease in c-myc transcripts. c-myc mRNA expression was reduced to a greater extent than was either beta-actin of GAPDH expression. Morphological, biochemical and ultrastructural evidence of apoptosis accompanied the Mafosfamide-induced c-myc mRNA down-regulation at 24 hours. We conclude that, in the context of Mafosfamide-treated HL-60 cells, upregulation of c-myc mRNA transcription was not fundamental for the activation of the apoptotic cascade.
Davidoff
A N
AN
Department of Haematology, School of Pathology, University of the Witwatersrand, Parktown, South Africa.
Mendelow
B V
BV
D000199:Actins / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000633:toxicity; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000199:Actins; D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C048341:mafosfamide; D003520:Cyclophosphamide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases