Combination of 5-deoxy-5-fluorouridine and tamoxifen show cell-type specific antagonistic and cooperative effects on cytotoxicity in human mammary carcinoma cells

Aliccia Bollig, Qian Qian Du, Shing Tzu Fan, Ben Yu, Fazlul H. Sarkar, Joshua Liao

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The effect of tamoxifen (Tarn) and 5-deoxy-5-fluorouridine (5-DFUR) cotreatment on cytotoxicity was assessed in various cancer-derived cell lines. Each cell line was treated with a range of Tam and 5-DFUR concentrations alone and in combination. The cell lines we examined include MDA-MB-231 (ERα-/ERβ+), T47D (ERα+/ ERβ+), and three MCF-7 (ERα+/ERβ +) sublines. Cell growth was assessed by MTT assay at multiple time points for up to 9 days. Fluorescence-associated cell sorting (FACS) analysis was used to examine the effects of Tam and 5-DFUR cotreatment on cell cycle progression. Treatment with Tarn or 5-DFUR, which is metabolized to 5-FU in target cells, produced an anti-proliferative effect that was dose- and time-dependent in all cell lines examined; variation in cell line sensitivity to each compound and cotreatment was apparent. When 5-DFUR and Tarn treatment were combined, T47D, MDA-MB-231, and an MCF-7 subline demonstrated a cooperative effect at the lowest Tam concentration tested in 9-day cultures. The significance of treatment dosage and duration was obvious when 5-DFUR and Tarn cotreatment was observed to be antagonistic in 3-day cultures of a second MCF-7 subline and T47D cells. Results from our studies show that there may be cytotoxic benefits in the treatment of cancer from combined therapy with Tarn and 5-FU precursor drugs. Enhanced inhibition of proliferation was observed when Tarn was cotreated at low concentrations in relatively long-term cultures. This has clinical relevance in that it suggests that patients undergoing chemo-endocrine therapy with orally administered 5-FU precursor drugs may benefit from lower treatment dosages relative to other adjuvant therapies.

Original languageEnglish (US)
Pages (from-to)177-183
Number of pages7
JournalOncology Reports
Volume14
Issue number1
StatePublished - Jul 1 2005

Keywords

  • 5-deoxy-5-fluorouridine
  • Breast cancer
  • Chemoendocrine
  • Chemotherapy
  • Tamoxifen

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