Biological activity in vitro of side-chain modified analogues of calcitriol.
The results of our studies on the biological activity of side-chain modified analogues of vitamin D are reviewed. These analogues appeared to be effective in induction of cell differentiation, inhibition of tumour cell proliferation in vitro and in increasing of antitumour effect of cytostatics. On the other hand, inhibition of cytostatic-induced apoptosis by these compounds was observed. The mechanism of the antiproliferative effect of calcitriol 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 differentiation of the HL-60 leukaemia cells induced by side-chain modified analogues 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 observed a synergistic antiproliferative effect of the combined therapy using analogues of calcitriol with subsequent treatment with the above-mentioned cytostatics. This effect was measured as a significant decrease of the ID50 values for each cytostatic applied after pretreatment of the tumour cells with the calcitriol analogues. The results presented suggest that the improved therapeutic effect may be achieved also in vivo by the combined application of the analogues (without calcemic activity) of calcitriol with antitumour agents.
Opolski
A
A
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12, Rudolf Weigl St., Wroclaw, 53-114, Poland. opolski@immuno.iitd.pan.wroc.pl
Wietrzyk
J
J
Siwinska
A
A
Marcinkowska
E
E
Chrobak
A
A
Radzikowski
C
C
Kutner
A
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000031:analogs & derivatives*; D002454:Cell Differentiation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002117:Calcitriol