1alpha,25-dihydroxyvitamin D(3) (Calcitriol) and Its Analogue, 19-nor-1alpha,25(OH)(2)D(2), Potentiate the Effects of Ionising Radiation on Human Prostate Cancer Cells

Br J Cancer. 2003 Aug 18;89(4):746-53. doi: 10.1038/sj.bjc.6601161.

Abstract

Radiotherapy with external beam radiation or brachytherapy is an established therapeutic modality for prostate cancer. Approximately 30% of patients with localised prostate cancer relapse at the irradiated site. Secondary effects of ionising radiation (IR), for example, bowel and bladder complications, are common. Thus, the search for biological response modifiers that could potentiate the therapeutic effects of radiation and limit the occurrence of serious side effects is an important task in prostate cancer therapy. 1alpha,25-Dihydroxyvitamin D(3) (calcitriol), the active metabolite of vitamin D, and its analogues are under investigation for the treatment of several malignancies including prostate cancer. Here, we report that 1alpha,25-dihydroxyvitamin D(3) and its less calcaemic analogue 19-nor-1alpha,25-(OH)(2)D(2) (Zemplar) act synergistically with IR to inhibit the growth of the human prostate cancer cells in vitro. 1alpha,25-dihydroxyvitamin D(3) potentiated IR-induced apoptosis of LNCaP cells, and nanomolar doses of 1alpha,25-dihydroxyvitamin D(3) and 19-nor-1alpha,25-(OH)(2)D(2) showed synergistic inhibition of growth of LNCaP cells at radiobiologically relevant doses of IR (1-2 Gy). At higher doses of IR, the combination of 1alpha,25-dihydroxyvitamin D(3) and IR or 19-nor-1alpha,25-(OH)(2)D(2) and IR resulted in moderate antagonism. The synergistic effect at radiobiologically relevant doses of radiation suggests that a combination of 1alpha,25-dihydroxyvitamin D(3) or 19-nor-1alpha,25-(OH)(2)D(2) with IR could permit a reduction in the dose of radiation given clinically and thus potentially reduce treatment-related morbidity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects
  • Blotting, Western
  • Calcitriol / pharmacology*
  • Cell Division
  • DNA, Neoplasm / chemistry
  • DNA, Neoplasm / genetics
  • Ergocalciferols / pharmacology*
  • Humans
  • Male
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Radiation, Ionizing
  • Radiation-Sensitizing Agents / pharmacology*
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Ergocalciferols
  • Radiation-Sensitizing Agents
  • paricalcitol
  • Calcitriol