The effects of 1α,24(S)-dihydroxyvitamin D2 analog on cancer cell proliferation and cytokine expression

Shraga Shany, Yfat Levy, Merav Lahav-Cohen

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


It is well established that 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), the active metabolite of vitamin D, plays a role in regulating proliferation and differentiation of cells, in addition to its classic function in mineral homeostasis. Recent studies have also provided evidence for the involvement of 1α,25(OH)2D3 in regulating the immune system. However, therapeutic application of 1α,25(OH)2D3 to hyperproliferative diseases such as cancer, or for immunologic purposes, is thwarted by its hypercalcemic activity. In order to overcome this obstacle, analogs of 1α,25(OH)2D3 have been produced that exhibit decreased hypercalcemic activity while retaining the growth and immunologic regulating properties. In the present study, the efficacy of 1α,24(S)-dihydroxyvitamin D2 (1α,24(S)(OH)2D2), a vitamin D2 analog, in restraining cell proliferation was compared to that of 1α,25(OH)2D3. In parallel studies, cancer cell lines were grown in increased concentrations (10-10-10-7 M) of each compound for various incubation periods (1-4 days). Growth was assessed by measuring [3H]thymidine incorporation. The results revealed that 1α,24(S)(OH)2D2 significantly inhibits proliferation to an extent similar to that observed for 1α,25(OH)2D3. Moreover, incubating the human leukemia cell line, HL-60, with 1α,24(S)(OH)2D2 resulted in an induction of differentiation of these promyelomonocyte cells into monocyte-macrophage-like cells, in a manner similar to that observed with 1α,25(OH)2D3. Using a Western procedure, it was also shown that 1α,24(S)(OH)2D2 like 1α,25(OH)2D3 enhances the expression of vitamin D receptors (VDR) in the rat osteosarcoma cell line, ROS 17/2.8. The expression of tumor necrosis factor (TNF) alpha (TNF-α) in human peritoneal macrophages (HPM) obtained from uremic patients treated with continuous ambulatory peritoneal dialysis (CAPD) was found to be regulated by 1α,25(OH)2D3 as well as by 1α,24(S)(OH)2D2. Incubations of HPM with 1α,25(OH)2D3 or 1α,24(S)(OH)2D2, have inhibited the expression of TNF-α on both mRNA and protein levels. These results suggest that 1α,25(OH)2D3 has a role in controlling the rate of inflammation in the peritoneal cavity of CAPD treated patients. Since 1α,24(S)(OH)2D2 does not cause hypercalcemia, the present results encourage the possible use of this vitamin D2 analog in the treatment of cancer and hyper-inflammatory diseases.

Original languageEnglish
Pages (from-to)319-325
Number of pages7
Issue number3-5
StatePublished - 1 May 2001


  • Cancer
  • Cancer cell lines
  • Cell proliferation
  • Cytokine
  • Rats
  • TNF-α
  • Vitamin D
  • Vitamin D analogs

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry


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