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

• Published in: Journal of cancer research and clinical oncology 1992-03, Vol.118 (3), p.190-194
• Main Authors: Clark, J W, Posner, M R, Marsella, J M, Santos, A, Uskokovic, M, Eil, C, Lasky, S R
• Format: Article
• Language: English
• Subjects: Antigens, CD - analysis; Antigens, Differentiation, Myelomonocytic - analysis; Calcitriol - analogs & derivatives; Calcitriol - pharmacology; Cell Differentiation - drug effects; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Lipopolysaccharide Receptors; Macrophage-1 Antigen - analysis; Structure-Activity Relationship; Tumor Cells, Cultured - drug effects
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/BF01410133

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.