INHIBITION OF HUMAN CANCER CELL-GROWTH BY 1,25-DIHYDROXYVITAMIN-D3 METABOLITES

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (9) , 4443-4447
Abstract
Specific high-affinity 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors, which can undergo hormone-dependent activation and nuclear localization, have been demonstrated in a wide variety of established human cancer cell lines and surgically obtained human cancer tissues. 1,25-(OH)2D3 has been reported by some workers to stimulate cancer cell replication at low physiological concentrations and by others to inhibit at higher concentrations. 1,25-(OH)2D3 had a biphasic effect on the replication of 2 distinct human cancer cell lines, i.e. the breast cancer T-47D and the malignant melanoma MM96. These inhibitory effects were accompanied by marked morphological changes. Furthermore, 2 known metabolites of 1,25-(OH)2D3, i.e., 1,24,25-trihydroxyvitamin D3 and 1,25,26-trihydroxyvitamin D3, which compete for binding to the 1,25-(OH)2D3 receptor, did not stimulate but were almost equipotent with 1,25-(OH)2D3 in inhibiting the replication of both cell lines. The stimulatory but not the inhibitory effect of 1,25-(OH)2D3 was abolished by cortisone. These 1,25-dihydroxyvitamin D3 metabolites show promise for the inhibition of cancer growth, analogous to the effect of estrogens and antiestrogens in breast cancer but with potential application in a much wider range of human cancers.

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