Inecalcitol, an analog of 1α,25(OH)(2) D(3) , induces growth arrest of androgen-dependent prostate cancer cells

Int J Cancer. 2012 May 15;130(10):2464-73. doi: 10.1002/ijc.26279. Epub 2011 Aug 27.


19-nor-14-epi-23-yne-1,25(OH)(2) D(3) (inecalcitol) is a unique vitamin D(3) analog. We evaluated the activity of inecalcitol in a human prostate cancer model system. The analog was 11-fold more potent than 1,25(OH)(2) D(3) in causing 50% clonal growth inhibition of androgen-sensitive human prostate cancer LNCaP cells. Inecalcitol, more than 1,25(OH)(2) D(3) , reduced in a dose-dependent manner the expression levels of the transcription factor ETS variant 1 and the serine/threonine protein kinase Pim-1, both of which are upregulated in prostate cancer. Remarkably, dose challenge experiments revealed that inecalcitol maximal tolerated dose (MTD) by intraperitoneal (i.p.) administration was 30 μg/mouse (1,300 μg/kg) three times per week, while we previously found that the MTD of 1,25(OH)(2) D(3) is 0.0625 μg/mouse; therefore, inecalcitol is 480 times less hypercalcemic than 1,25(OH)(2) D(3) . Pharmacokinetic studies showed that plasma half-life of inecalcitol were 18.3 min in mice. A xenograft model of LNCaP cells was developed in immunodeficient mice treated with inecalcitol. The tumors of the diluent-treated control mice increased in size but those in the inecalcitol treatment group did not grow. Our data suggest that inecalcitol inhibits androgen-responsive prostate cancer growth in vivo and should be examined either alone or with other chemotherapy in clinical trials in individuals with rising serum prostate-specific antigen after receiving either surgery or irradiation therapy with curative intent.

MeSH terms

  • Alkynes / therapeutic use*
  • Androgens / physiology*
  • Animals
  • Cell Line, Tumor
  • Cholecalciferol / analogs & derivatives*
  • Cholecalciferol / therapeutic use
  • Humans
  • Male
  • Mice
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Alkynes
  • Androgens
  • inecalcitol
  • Cholecalciferol