Inhibition of c-myc in breast and ovarian carcinoma cells by 1,25-dihydroxyvitamin D3, retinoic acid and dexamethasone

Anticancer Drugs. 1993 Apr;4(2):201-8. doi: 10.1097/00001813-199304000-00012.


The role and regulation of the c-myc protooncogene in breast and ovarian neoplasms is receiving increased attention. The downregulation of the c-myc protooncogene by 1,25-dihydroxyvitamin D3 (calcitriol), retinoic acid (RA) and dexamethasone (Dex) is closely associated with growth inhibition in leukemic cells. Calcitriol, RA and Dex have anti-proliferative activity in breast and gynecologic carcinoma cells; however, the regulation of c-myc by these agents in breast and ovarian cancers is mostly unknown. We have addressed the regulation of c-myc in these cancers using an adaptation of a novel method which employs an immunohistochemical procedure to detect c-myc protein followed by quantification of c-myc staining with computerized image analysis. This system represents an alternative to protein product assay by Western blotting and is straightforward, rapid (1 day), can be carried out on a small scale and provides a sample size that readily facilitates statistical analysis of assay data. In MCF-7 human breast cancer cells, c-myc was suppressed 29% by 0.5 nM Dex, 45% by 0.01 nM RA and 54% by 100 nM calcitriol after 24 h of drug treatment. At the same hormone concentrations, growth was inhibited 18% by Dex, 18% by RA and 39% by calcitriol after 3 days of treatment (p < 0.05 for all hormones). Similar patterns of growth and c-myc inhibition were seen in T47D human breast cancer cells and NIH:OVCAR3 human ovarian cancer cells, with the exception of Dex in T47D cells, which caused no inhibition of c-myc or growth.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Blotting, Western
  • Breast Neoplasms / genetics*
  • Calcitriol / pharmacology*
  • Cell Division
  • Depression, Chemical
  • Dexamethasone / pharmacology*
  • Female
  • Gene Expression / drug effects
  • Genes, myc / drug effects*
  • Humans
  • Immunohistochemistry
  • Ovarian Neoplasms / genetics*
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured


  • Tretinoin
  • Dexamethasone
  • Calcitriol