EFFECTS OF ACLARUBICINE ON GROWTH, DIFFER ENTIATION AND APOPTOSIS OF TUMOR-CELLS IN-VITRO

Aclarubicine induces various effects after several days of incubation with human leukemic cells HL60: cell growth inhibition, inductions of differentiation, necrosis and apoptosis. Several methods of detection of differentiated and apoptotic cells were studied. The methods utiliz ing optical microscopy were used as references. Flow cytometry (FCM) a ppeared to have a higher sensitivity, but it yielded somewhat differen t results. Aclarubicine and doxorubicin have dose-dependent effects, e xcept for the differentiation induction by aclarubicine, which had a m aximum effect and then decreased; this probably means that the inducti ons of differentiation and apoptosis could be independent. Different k inetic studies indicated that differentiation increased quickly after 24 to 48 hours and reached a plateau toward 72 hours, where approximat ely 80% of the cells were differentiated. Necrosis increased at the sa me time, but less, with a 1 hour incubation with 75 nmol/l of aclarubi cine. Apoptosis appeared in an irregular and non-reproducible manner. The kinetic study also indicated a certain independence between the di fferentiation and apoptosis inductions.