Tamoxifen and tranilast show a synergistic effect against breast cancer in vitro

Bratisl Lek Listy. 2015;116(1):69-73. doi: 10.4149/bll_2015_013.

Abstract

Objective: This study was aimed at examining a separate or combined effect of tamoxifen and tranilast drugs on growth and proliferation of breast cancer cells.

Background: Breast cancer is one of the most common cancers and the second leading cause of cancer death among women worldwide. Tamoxifen is the most widely used anti-estrogen for the treatment of breast cancer. Studies show that a combination therapy with other drugs enhances the activity of tamoxifen. Tranilast is an anti-inflammatory drug. We hypothesize that tranilast plus tamoxifen can work synergistically and help getting better result from this anticancer drug.

Methods: Two breast cancer cell lines, MCF-7 and MDA-MB-231, were treated with graduated concentrations of tamoxifen and tranilast alone or in combination at 24, 48 or 72 hours for MCF-7, and 48 hours for MDA-MB-231 cells. We used the MTT assay and lactate dehydrogenase leakage (LDH) assay to evaluate cell viability and cytotoxicity, respectively.

Results: In both ER-positive and ER-negative breast cancer cell lines, the combination of tranilast and tamoxifen was more effective in growth inhibition than single drug exposure.

Conclusion: We have demonstrated that by means of a synergistic/additive inhibitory effect, tranilast was capable of enhancing the in vitro activity of tamoxifen on breast cancer cell lines. Based on the results obtained in this study, tranilast could be a candidate drug for combination therapy in resistant breast cancer patients (Fig. 9, Ref. 17).

Keywords: breast cancer, Tamoxifen, Tranilast, LDH release, MTT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Synergism
  • Female
  • Humans
  • Tamoxifen / administration & dosage*
  • Tumor Cells, Cultured
  • ortho-Aminobenzoates / administration & dosage*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents, Hormonal
  • ortho-Aminobenzoates
  • Tamoxifen
  • tranilast