1,25-Dihydroxyvitamin D inhibits vitamin E succinate-induced apoptosis in C3H10T1/2 cells but not Harvey ras-transfected cells

Lynn Stedman, Kwangok P. Nickel, S. Sianna Castillo, Juan Andrade, John R. Burgess, Dorothy Teegarden

Research output: Contribution to journalArticle

Abstract

In this study, the effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on regulation of apoptosis was compared in control C3H1OT1/2 mouse fibroblast cells and those transfected with the Harvey ras oncogene. A known apoptotic stimulator, vitamin E succinate (VES), reduced cell number in a time- and dose-dependent manner in both cell types. In an assay for viable cells, there were significantly more C3H10T1/2 cells cotreated with VES and 1,25(OH)2D3 (-5.0 ± 10.5% of vehicle-treated controls) compared to VES alone treated cells (-60.8 ± 5.6%). In contrast, 1,25(OH)2D3 did not change the percentage of viable cells following treatment by VES in ras-transfected cells [-67.3 ± 7.5%, VES alone compared to 57.3 ± 15.7% with VES and 1,25(OH)2D3]. Further studies confirmed that 1,25(OH)2D3 inhibited VES-mediated apoptosis (1.27 ± 0.34-fold over vehicle control) compared to VES treatment alone (2.29 ± 0.56-fold increase) in C3H10T1/2 cells, but not in ras-transfected cells [3.07 ± 0.43-fold increase, VES treatment alone; 3.64 ± 0.42-fold increase, VES and 1,25(OH)2D3]. Both C3H10T1/2 and ras-transfected cells treated with VES had increased concentrations of cellular VES with very little change in a-tocopherol, indicating that the cells took up VES intact. In addition, both cell lines contained similar levels of nuclear vitamin D receptor (VDR); however, the ras-transfected cells had reduced VDRE transcriptional activity. In conclusion, VES exerts its effect intact and 1,25(OH)2D3 preferentially protects C3H10T1/2 cells, whereas ras-transformed cells were not protected from VES-mediated apoptosis.

Original languageEnglish (US)
Pages (from-to)93-100
Number of pages8
JournalNutrition and Cancer
Volume45
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

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