Antiproliferative activity in vitro of side-chain analogues of calcitriol against various human normal and cancer cell lines

The antiproliferative in vitro activity of side-chain modified analogues of 1,25-dihydroxyvitamin D-3 was examined in order to select compounds with p otential antitumor activity. Analogues PRI-1906, PRI-1907, PRI-1909, PRI-21 91, PRI-2192, PRI-2193 and PRI-2194 were examined for their antiproliferati ve activity in vitro against a spectrum of various human cancer cell lines using the MTT technique. In addition, analogues PRI-1906 and PRI-2191 were screened against cells of human leukaemia HL-60 line and against normal hum an skin fibroblasts. Calcitriol and these two analogues revealed strong ant iproliferative activity against these two targets with maximal growth inhib ition of 68% for HL-60 cells and of 60% for fibroblasts, and this effect wa s dose dependent. All analogues tested except PRI-1909, revealed antiprolif erative activity against human carcinoma cell lines of breast origin applie d namely against T47D and MCF-7. The maximal growth inhibition of 49% for T 47D cell line and 39% for MCF-7 line was observed, and this effect was clos e dependent. The inhibitory doses of the analogues tested were compared wit h the indices for calcitriol. Analogue PRI-1906 revealed the strongest anti proliferative activity against these fern target cell lines (HL-60, fibrobl asts, MCF-7, and T47D). The novel analogues of calcitriol, similarly to cal citriol, appeared to be not active against other human cancer cell lines te sted (including those originated from lung, colon, prostate, urinary bladde r; ovary pancreas, stomach and kidney) revealing an antiproliferative activ ity nor exceeding 20%. The mechanism of the observed antiproliferative effe ct of calcitriol and its analogues in vitro remains unclear; however; it ma y be related to their effect on cell differentiation. The appearance of ant igen CD14 and CD11b expression after exposure to calcitriol and its new ana logues confirmed their effect on cell differentiation.