Anti-Cancer Effects of Sulfasalazine and Vitamin E Succinate in MDA-MB 231 Triple-Negative Breast Cancer Cells

Int J Med Sci. 2019 Mar 9;16(4):494-500. doi: 10.7150/ijms.30380. eCollection 2019.

Abstract

Aim: Sulfasalazine (SSZ) displayed anti-cancer activities. Vitamin E succinate (VES) could inhibit cell growth in various cancer cells. However, chemical therapies were often not useful for triple-negative breast cancer cells (TNBCs) treatment. Here, this study investigated the anti-cancer effects and the mechanisms on TNBCs under combination treatment with SSZ and VES. Methods: Cell viability was analyzed by using the MTT assay. The H2O2 levels were determined by using lucigenin-amplified chemiluminescence method. In addition, caspase and MAPs signals were studied by using western blotting. Results: Low-dose VES antagonized the SSZ-induced cytotoxicity effects while high-dose VES promoted the SSZ-induced cytotoxicity effects on TNBCs. In addition, SSZ alone treatment activated both caspase-3 and ERK signals, however, VES alone treatment only activated JNK signals. On the other hand, activation of caspase-3, JNK, and ERK were found in SSZ plus VES-treated cells. Conclusion: Combined SSZ and VES has synergistic or antagonistic cytotoxic effects depending on VES concentration. In addition, different cytotoxic signals are induced on SSZ-treated, VES-treated and SSZ plus VES-treated cells.

Keywords: sulfasalazine; triple-negative breast cancer cells; vitamin E succinate.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hydrogen Peroxide / isolation & purification
  • MAP Kinase Kinase 4 / genetics
  • Signal Transduction / drug effects
  • Sulfasalazine / pharmacology*
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology
  • alpha-Tocopherol / pharmacology*

Substances

  • Sulfasalazine
  • Hydrogen Peroxide
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase 4
  • Caspase 3
  • alpha-Tocopherol