1α,25-Dihydroxyvitamin D3 (calcitriol) and its analogue, 19-nor-1α,25(OH)2D2, potentiate the effects of ionising radiation on human prostate cancer cells

N. Dunlap, G. G. Schwartz, D. Eads, S. D. Cramer, A. B. Sherk, V. John, C. Koumenis

Research output: Contribution to journalArticle

59 Scopus citations

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. 1α,25-Dihydroxyvitamin D3 (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 1α,25-dihydroxyvitamin D3 and its less calcaemic analogue 19-nor-1α,25-(OH)2D2 (Zemplar®) act synergistically with IR to inhibit the growth of the human prostate cancer cells in vitro. 1α,25-dihydroxyvitamin D3 potentiated IR-induced apoptosis of LNCaP cells, and nanomolar doses of 1α ,25-dihydroxyvitamin D3 and 19-nor-1α,25-(OH)2D 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 1α,25-dihydroxyvitamin D3 and IR or 19-nor-1α,25-(OH)2D2 and IR resulted in moderate antagonism. The synergistic effect at radiobiologically relevant doses of radiation suggests that a combination of 1α,25-dihydroxyvitamin D 3 or 19-nor-1α,25-(OH)2D2 with IR could permit a reduction in the dose of radiation given clinically and thus potentially reduce treatment-related morbidity.

Original languageEnglish (US)
Pages (from-to)746-753
Number of pages8
JournalBritish journal of cancer
Volume89
Issue number4
DOIs
StatePublished - Aug 18 2003

Keywords

  • Radiosensitizer
  • Synergistic
  • Vitamin D
  • Zemplar

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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