Anticancer and apoptotic activities of parthenolide in combination with epirubicin in mda-mb-468 breast cancer cells

Mol Biol Rep. 2020 Aug;47(8):5807-5815. doi: 10.1007/s11033-020-05649-3. Epub 2020 Jul 20.

Abstract

Breast cancer is the most common malignancy in women worldwide. Unfortunately, current therapeutic methods are not completely efficient. Hence, combination therapy with medicinal plants has attracted several kinds of research. In the current study, we aimed to investigate the apoptotic and anti-cancer effect of Parthenolide in combination with Epirubicin in the MDA-MB-468 breast cancer cell line. In this study, the anti-proliferative and pro-apoptotic effect of Parthenolide in combination with Epirubicin and without it, in the MDA-MB-468 cell line have been assessed by MTT test, Hoescht staining and flow cytometry methods. Our outcomes showed that Parthenolide treatment in the present of Epirubicin led to a decrease in the minimum toxic concentration of Parthenolide and Epirubicin in comparison with individual treatments. Then, to achieve a likely molecular mechanism of mentioned drugs Bax and Bcl2 expression level evaluated by Real-time PCR and subsequently, Western blotting has been estimated the protein level of Caspase 3. Our data indicated that the treatment of cells with Parthenolide led to up-regulation of Bax and downregulation of Bcl2 at mRNA level. Moreover, Parthenolide treatment led to the obvious alternation of Caspase3 protein level. These results indicated that Parthenolide in combination with Epirubicin have significant cytotoxicity due to targeting the main regulators of apoptosis. Hence, according to lack of cytotoxicity of Parthenolide on normal cells that lead to reduction of drug side effects, it could be suggested as an adjuvant therapy with Epirubicin after complementary research on animal model and clinical trial.

Keywords: Apoptosis; Breast cancer; Epirubicin; Parthenolide.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Epirubicin / administration & dosage
  • Female
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Sesquiterpenes / administration & dosage
  • Topoisomerase II Inhibitors / administration & dosage
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • BAX protein, human
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Sesquiterpenes
  • Topoisomerase II Inhibitors
  • bcl-2-Associated X Protein
  • parthenolide
  • Epirubicin