The antiproliferative in vitro activity of side-chain modified analogues of
1,25-dihydroxyvitamin D3 was examined in order to select compounds with potential antitumour activity. Analogues
PRI-1906,
PRI-1907, PRI-1909,
PRI-2191, PRI-2192, PRI-2193 and PRI-2194 were examined for their antiproliferative 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 human skin fibroblasts.
Calcitriol and these two analogues revealed strong antiproliferative activity against these two targets with maximal growth inhibition of 68% for HL-60 cells and of 60% for fibroblasts, and this effect was dose dependent. All analogues tested, except PRI-1909, revealed antiproliferative activity against human
carcinoma cell lines of breast origin applied, namely against T47D and MCF-7. The maximal growth inhibition of 49% for T47D cell line and 39% for MCF-7 line was observed, and this effect was dose dependent. The inhibitory doses of the analogues tested were compared with the indices for
calcitriol. Analogue
PRI-1906 revealed the strongest antiproliferative activity against these four target cell lines (HL-60, fibroblasts, MCF-7, and T47D). The novel analogues of
calcitriol, similarly to
calcitriol, appeared to be not active against other human
cancer cell lines tested (including those originated from lung, colon, prostate, urinary bladder, ovary, pancreas, stomach and kidney) revealing an antiproliferative activity not exceeding 20%. The mechanism of the observed antiproliferative effect of
calcitriol and its analogues in vitro remains unclear, however, it may be related to their effect on cell differentiation. The appearance of
antigen CD14 and CD11b expression after exposure to
calcitriol and its new analogues confirmed their effect on cell differentiation.