Evaluation of C-2-substituted 19-nor-1α,25-dihydroxyvitamin D3 analogs as therapeutic agents for prostate cancer

T. C. Chen, K. S. Persons, S. Zheng, J. Mathieu, M. F. Holick, Y. F. Lee, B. Bao, M. A. Arai, A. Kittaka

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) is known to inhibit the proliferation and invasiveness of prostate cancer cells. However, 1α,25(OH)2D3 can cause hypercalcemia and is not suitable as a therapeutic agent. 19-Nor-vitamin D derivatives are known to be less calcemic when administered systemically. In order to develop more potent anti-cancer agents with less calcemic side effect, we therefore utilized 3H-thymidine incorporation as an index for cell proliferation and examined the antiproliferative activities of nine C-2-substituted 19-nor-1α,25(OH)2D3 analogs in the immortalized PZ-HPV-7 normal prostate cell line. Among the nine analogs we observed that the substitution with 2α- or 2β-hydroxypropyl group produced two analogs having antiproliferative potency that is approximately 500- to 1000-fold higher than 1α,25(OH)2D3. The 3H-thymidine incorporation data were supported by the cell counting data after cells were treated with 1α,25(OH)2D3, 19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3 or 19-nor-2β-(3-hydroxypropyl)-1α,25(OH)2D3 for 7 days. 19-Nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3 and 19-nor-2β-(3-hydroxypropyl)-1α,25(OH)2D3 were also shown to be about 10-fold more active than 1α,25(OH)2D3 in cell invasion studies using prostate cancer cells. In conclusion, a substitution at the C-2 position of 19-nor-1α,25(OH)2D3 molecule with a hydroxypropyl group greatly increased the antiproliferative and anti-invasion potencies. Thus, these two analogs could be developed to be effective therapeutic agents for treating early and late stages of prostate cancer.

Original languageEnglish
Pages (from-to)717-720
Number of pages4
JournalJournal of Steroid Biochemistry and Molecular Biology
Issue number3-5
Publication statusPublished - 2007 Mar
Externally publishedYes


  • Analog
  • Invasion
  • PC-3
  • PZ-HPV-7
  • Proliferation
  • Prostate cancer
  • Vitamin D

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology


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