Induction of differentiation in Friend-erythroleukemia cells by aclacinomycin A: early transient decrease in c-myc and c-myb mRNA levels.

Chemical inducers of the differentiation are known to cause an early transient decrease in c-myc and c-myb mRNA levels in Friend erythroleukemia cells preceding the down-regulation of c-myc and c-myb expression in the course of irreversible terminal differentiation. We therefore investigated the early effect of the potent differentiation-inducing anthracycline antitumor antibiotic, aclacinomycin A, on the c-myc and c-myb mRNA levels in the Friend cell line, F4-6, using Northern blot analysis. Aclacinomycin A induced a rapid decrease in the levels of c-myc and c-myb transcripts within 0.5-1 h and 2-3 h, respectively. The time course of decline in c-myc and c-myb expression was similar to that observed with dimethylsulfoxide or after transcription blockage brought about by a high concentration of actinomycin D. By 12 to 18 h after aclacinomycin A exposure, the c-myc and c-myb mRNA levels had returned to about pretreatment levels. When the cells were treated with adriamycin, an anthracycline that reduces cell proliferation in F4-6 cells without increasing differentiation, an early decrease in c-myc and c-myb expression was not observed. These results suggest that the transient decrease in c-myc and c-myb mRNA levels in F4-6 cells may be an early differentiation-related biochemical effect of aclacinomycin A.