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  • Title: Effects of analogs of 1,25(OH)2 vitamin D3 on the proliferation and differentiation of the human chronic myelogenous leukemia cell line, RWLeu-4.
    Author: Clark JW, Posner MR, Marsella JM, Santos A, Uskokovic M, Eil C, Lasky SR.
    Journal: J Cancer Res Clin Oncol; 1992; 118(3):190-4. PubMed ID: 1372318.
    Abstract:
    We evaluated the proliferative and differentiative effects of analogs of 1,25(OH)2 vitamin D3 [1,25(OH)2D3] on a chronic myelogenous leukemia cell line, RWLeu-4, which is growth-inhibited and differentiates in response to 1,25(OH)2D3 (ED50 = 3-10 nM). Side-chain-fluorinated analogs were more potent (ED50 = 0.7-2 nM) while most of those with altered saturation of the D ring or side-chain carbon-carbon bonds were equally or less effective than 1,25(OH)2D3. However, the two analogs with either two additional double bonds or an extra double and triple bond in the D ring had greater antiproliferative activity [1,25(OH)2-16,23-diene D3 (ED50 = 2.7 nM) and 1,25(OH)2-16-ene-23-yne D3 (ED50 = 0.7 nM)]. Since the latter of these has been reported to be less potent at mobilizing calcium than 1,25(OH)2D3, it (or a similar compound) may be a candidate for clinical use as an antineoplastic agent.
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