The novel analog 1,24(S)-dihydroxyvitamin D2 is as equipotent as 1,25-dihydroxyvitamin D3 in growth regulation of cancer cell lines.
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.
Department of Clinical Biochemistry, Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel.
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Levy
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Knutson
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Bishop
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Shany
D000818:Animals; D001854:Bone Marrow Cells; D001859:Bone Neoplasms; D001943:Breast Neoplasms; D002117:Calcitriol / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D002645:Chickens; D003110:Colonic Neoplasms; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004872:Ergocalciferols / Q000633:toxicity*; D005260:Female; D016259:Genes, myc; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D012516:Osteosarcoma; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004872:Ergocalciferols; C063087:1,24-dihydroxyvitamin D2; D002117:Calcitriol