Influence of vitamin D3 metabolites on cell proliferation and cytotoxicity of adriamycin in human normal and neoplastic cells.
The common features of biological activity displayed by vitamin D family members and adriamycin suggest the possibility of synergistic effects of the combination of these compounds. Until now, the mechanisms responsible mainly for adriamycin cytotoxic action have not been indicated. Therefore, observation of the possible common cell targets for adriamycin and vitamin D metabolites could shed more light on the mechanisms of cytotoxic activity of adriamycin. In the present study, the influence of calcidiol (25-hydroxyvitamin D(3)) and calcitriol (1alpha,25-dihydroxyvitamin D(3)) on the proliferation and cytotoxicity of adriamycin was studied. The following cell lines were tested: normal human fibroblasts-CRL 1502, human melanoma cells-ME18 and its subline-ME18/R, resistant to adriamycin. As was shown, 72 h of incubation with calcidiol or calcitriol, both at 10 microM, inhibited growth (to approx. 60%) only of the ME18 cells. Dose and time dependence of this effect has been confirmed. Antiproliferative events did not correlate with an increase of adriamycin cytotoxicity. It was noted that calcidiol and calcitriol had no significant influence on the adriamycin IC(50) values in any cell lines tested. These results point to the divergent mechanisms of action of adriamycin and vitamin D(3) metabolites.
Gruber
B M
BM
Department of Vitamin Drugs, Drug Institute, 30/34 Chelmska Str., 00-725 Warsaw, Poland.
Anuszewska
E L
EL
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D002112:Calcifediol / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology* / Q000633:toxicity; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D005347:Fibroblasts; D006801:Humans; D007928:Lethal Dose 50; D008545:Melanoma / Q000473:pathology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004317:Doxorubicin; D002117:Calcitriol; D002112:Calcifediol