The novel analog 1,24(S)-dihydroxyvitamin D2 is as equipotent as 1,25-dihydroxyvitamin D3 in growth regulation of cancer cell lines.
1998
The physiologically active metabolite of the vitamin D seco-steroid hormone, 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), 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) 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 hypercalcemic activity. In the present study, the efficacy of the vitamin D 2 analog, 1,24(S)-dthydroxyvitamin D 2 (1,24(S)-(OH) 2 D 2 ) in the inhibition of cancer cell proliferation and in inducing differentiation of cancer cells was compared to that of 1,25(OH) 2 D 3 By the [ 3 H]-thymidine 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 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) 2 D 2 induces the differentiation of the human leukemia cell (HL-60) to the same extent as 1,25(OH) 2 D 3 . Notwithstanding the vast similarity between 1,24(S)-(OH)2D2 and 1,25(OH) 2 D 3 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) 2 D 2 for the treatment of cancer diseases in vivo.
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