Summary
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 antiproliferatiive 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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Abbreviations
- 1,25(OH)2D3 :
-
1α,25-(OH)2 vitamin D3
- CML:
-
chronic myelogenous leukemia
- NBT:
-
nitroblue tetrazolium
- ED50 :
-
50% effective dose
- IC50 :
-
50% inhibitory concentration
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Clark, J.W., Posner, M.R., Marsella, J.M. et al. 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. J Cancer Res Clin Oncol 118, 190–194 (1992). https://doi.org/10.1007/BF01410133
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DOI: https://doi.org/10.1007/BF01410133