Potentiation of cell killing by fractionated radiation and suppression of proliferative recovery in MCF-7 breast tumor cells by the Vitamin D3 analog EB 1089

Gerald A. DeMasters, Mona S. Gupta, Kara R. Jones, Myles Cabot, Hongtao Wang, Chris Gennings, Misook Park, Åse Bratland, Anne H. Ree, David A. Gewirtz

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

A senescence-like growth arrest succeeded by recovery of proliferative capacity was observed in MCF-7 breast tumor cells exposed to fractionated radiation, 5 × 2 Gy. Exposure to EB 1089, an analog of the steroid hormone 1α, 25 dihydroxycholecalciferol (1α, 25 dihydroxy Vitamin D 3; calcitriol), prior to irradiation promoted cell death and delayed both the development of a senescent phenotype and the recovery of proliferative capacity. EB 1089 also reduced clonogenic survival over and above that produced by fractionated radiation alone and further conferred susceptibility to apoptosis in MCF-7 cells exposed to radiation. In contrast, EB 1089 failed to enhance the response to radiation (or to promote apoptosis) in normal breast epithelial cells or BJ fibroblast cells. EB 1089 treatment and fractionated radiation additively promoted ceramide generation and suppressed expression of polo-like kinase 1. Taken together, these data indicate that EB 1089 (and 1α, 25 dihydroxycholecalciferol or its analogs) could selectively enhance breast tumor cell sensitivity to radiation through the promotion of cell death, in part through the generation of ceramide and the suppression of polo-like kinase.

Original languageEnglish
Pages (from-to)365-374
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume92
Issue number5
DOIs
StatePublished - Dec 2004
Externally publishedYes

Keywords

  • Apoptosis
  • Breast cancer
  • Ceramide
  • Radiation
  • Vitamin D

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