Levy Y, Knutson J C, Bishop C, Shany S
Department of Clinical Biochemistry, Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel.
Anticancer Res. 1998 May-Jun;18(3A):1769-75.
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.
维生素D甾体激素的生理活性代谢产物1,25 - 二羟基维生素D3（1,25(OH)2D3）是矿物质稳态的主要调节因子。最近的证据还表明其在调节包括癌细胞在内的细胞增殖和分化中发挥作用。1,25(OH)2D3对增殖性疾病如癌症的治疗应用因其高钙血症活性而受到阻碍。为克服这一问题，已制备出1,25(OH)2D3的类似物，它们保留了生长调节特性且高钙血症活性降低。在本研究中，将维生素D2类似物1,24(S)-二羟基维生素D2（1,24(S)-(OH)2D2）抑制癌细胞增殖和诱导癌细胞分化的功效与1,25(OH)2D3进行了比较。通过[3H]-胸苷掺入法，1,24(S)-(OH)2D2在抑制五种不同细胞系（ROS 17/2.8，大鼠骨肉瘤细胞系；MCF-7，人乳腺癌细胞系；HD-11，鸡骨髓v-myc转化细胞系；HT-29，人结肠癌细胞系；HL-60，人白血病细胞系）的增殖方面与1,25(OH)2D3具有同等效力。抑制作用呈剂量和时间依赖性。NBT还原法表明，1,24(S)-(OH)2D2诱导人白血病细胞（HL-60）分化的程度与1,25(OH)2D3相同。尽管1,24(S)-(OH)2D2和1,25(OH)2D3在上述活性方面极为相似，但它们对钙调节的作用不同。总之，目前的结果支持在体内使用1,24(S)-(OH)2D2治疗癌症疾病。
