Potentiation of the antiproliferative effect in vitro of doxorubicin, cisplatin and genistein by new analogues of vitamin D

Numerous vitamin D-3 analogues have been synthesised in recent years in ord er to obtain compounds with a favourable biological and therapeutic (antips oriatic and/or antitumour) activity. Our results showed that pre-treatment for 72 hours of HL-60 human promyelocytic leukaemia cells with calcitriol o r its new analogues significantly potentiated their sensitivity to the anti proliferative effect in vitro of cisplatin, doxorubicin or genistein. Moreo ver, for all cytotoxic agents tested a synergistic antiproliferative effect was observed. This effect was expressed as a significant decrease of the I D50 (inhibitory dose 50%) values for each cytotoxic agent applied after pre treatment with calcitriol or its analogues of HL-60 cells in comparison wit h the effect of cytotoxic agent applied alone. The observed in vitro potent iated antiproliferative effect of cytotoxic drugs used in combination with vitamin D or its analogues may raise the question as to whether such an eff ect could be expected in the in vivo situation.