The physiologically active metabolite of the
vitamin D seco-
steroid hormone,
1,25-dihydroxyvitamin D3 (
1,25(OH)2D3), is a major regulator of
mineral homeostasis. Recent evidence also suggests its role in regulating proliferation and differentiation of cells, including
cancer cells. Therapeutic application of
1,25(OH)2D3 to hyperproliferative disease, such as
cancer, is thwarted by its hypercalcemic activity. To overcome this problem, analogs of
1,25(OH)2D3 have been produced which retain growth regulating properties and exhibit decreased hypercalcemic activity. In the present study, the efficacy of the
vitamin D2 analog,
1,24(S)-dihydroxyvitamin D2 (1,24(S)-(OH)2D2) in the inhibition of
cancer cell proliferation and in inducing differentiation of
cancer cells was compared to that of
1,25(OH)2D3. By the [3H]-
thymidine incorporation procedure, 1,24(S)-(OH)2D2 is as equipotent as
1,25(OH)2D3 in inhibiting the proliferation of five different cell lines, ROS 17/2.8, the rat
osteosarcoma cell line, MCF-7, the human
breast cancer cell line, HD-11, the chick bone marrow v myc transformed cell line, HT-29, the human
colon cancer cell line and HL-60, the human
leukemia cell line. The inhibitory action was dose and time-dependent. The NBT reduction method indicated that 1,24(S)-(OH)2D2 induces the differentiation of the human
leukemia cell (HL-60) to the same extent as
1,25(OH)2D3. Notwithstanding the vast similarity between 1,24(S)-(OH)2D2 and
1,25(OH)2D3 with regard to the above activities, they differ in their effects on
calcium regulation. In conclusion, the present results encourage the use of 1,24(S)-(OH)2D2 for the treatment of
cancer disease in vivo.