The effect of new anthracycline derivatives on the induction of apoptotic processes in human neoplastic cells.
This study was an attempt to determine the effect of a selected anthracycline derivative, WP903, on apoptotic processes in human melanoma cells depending on intracellular concentrations of the compound, and to evaluate the significance of apoptosis induction for the cytotoxic effect of anthracycline antibiotics. It was found that the WP903, contrary to ADR (adriamycin) is a strong inducer of apoptotic processes in ME18 human melanoma cells regardless of their susceptibility to adriamycin and WP903. The cells were treated for 24 h with ADR (1 and 5 microg/ml) or WP903 (0.2 and 2 microg/ml). Apoptosis was detected with the use of annexin V-FITC and PI (propidium iodide) and with TUNEL assay. WP903 used at 0.2 microg/ml induced early apoptosis in 23% of ME18 cells and in 60% of ME18/R cells; at 2 microg/ml in 70% of each of cell line tested. Significant late apoptotic effect was observed in ME18 cells. In contrast, ADR was found to be a weak inducer of apoptotic events. The results suggest that apoptosis is not a mechanism directly related to the cytotoxic effect of anthracycline antibiotics.
Gruber
Beata M
BM
Department of Biochemistry and Biopharmaceuticals, National Institute of Public Health, Warsaw, Poland. b-gruber@il.waw.pl
Anuszewska
Elzbieta L
EL
Priebe
Waldemar
W
D018943:Anthracyclines / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology
D018943:Anthracyclines; D004317:Doxorubicin