Biological activity in vitro of side-chain modified analogues of calcitriol

The results of our studies on the biological activity of side-chain modifie d analogues of vitamin D are reviewed. These analogues appeared to be effec tive in induction of cell differentiation, inhibition of tumour cell prolif eration in vitro and in increasing of antitumour effect of cytostatics. On the other hand, inhibition of cytostatic-induced apoptosis by these compoun ds was observed. The mechanism of the antiproliferative effect of calcitrio l analogues in vitro is discussed. The induction of antigens CD14 and CD11b expression and phagocytic activity of HL-60 cells after exposure to these compounds is related to their effect on cell differentiation. The different iation of the HL-60 leukaemia cells induced by side-chain modified analogue s of calcitriol increases their sensitivity to the antiproliferative effect of cisplatin, doxorubicin and genistein, despite of that this pretreatment causes resistance of these cells to cytostatics-induced apoptosis. We obse rved a synergistic antiproliferative effect of the combined therapy using a nalogues of calcitriol with subsequent treatment with the above-mentioned c ytostatics. This effect was measured as a significant decrease of the ID50 values for each cytostatic applied after pretreatment of the tumour cells w ith the calcitriol analogues.