THE NOVEL ANALOG 1,24(S)-DIHYDROXYVITAMIN D-2 IS AS EQUIPOTENT AS 1,25-DIHYDROXYVITAMIN D-3 IN GROWTH-REGULATION OF CANCER CELL-LINES

The physiologically active metabolite of the vitamin D seco-steroid ho rmone, 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3), is a major regulato r of mineral homeostasis. Recent evidence also suggests its role in re gulating proliferation and differentiation of cells, including cancer cells. Therapeutic application of 1,25(OH)(2)D-3 to hyperproliferative diseases, such as cancer, is thwarted by its hypercalcemic activity. To overcome this problem, analogs of 1,25(OH)(2)D-3 have been produced which retain growth regulating properties and exhibit decreased hyper calcemic activity. In the present study, the efficacy of the vitamin D -2 analog, 1,24(S)-dihydroxyvitamin D-2 (1,24(S)-(OH)(2)D-2) in the in hibition of cancer cell proliferation and in inducing differentiation pf cancer cells was compared to that of 1,25(OH)(2)D-3. By the [H-3]-t hymidine incorporation procedure, 1,24(S)-(OH)(2)D-2 is as equipotent as 1,25(OH)(2)D-3 in inhibiting the proliferation of five different ce ll lines, ROS 17/2.8, the rat osteosarcoma cell line, MCF-7, the human breast cancer cell line, HD-II, the chick bone marrow nu myc transfor med 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-depe ndent. The NET reduction method indicated that 1,24(S)(OH)(2)D-2 induc es the differentiation of the human leukemia cell (HL-60) to the same extent as I,25(OH)(2)D-3. Notwithstanding the vast similarity between 1,24(S)-(OH)(2)D-2 and 1,25(OH)(2)D-3 with regard to the above activit ies, they differ in their effects on calcium regulation. In conclusion , the present results encourage the use of 1,24(S)-(OH)(2)D-2 for the treatment of cancer diseases in vivo.