Heat shock protein 90α inhibitor, PU-H71 in combination with DHEA promoting apoptosis in triple-negative breast cancer cell line MDA-MB-231

Acta Biochim Pol. 2020 Dec 15;67(4):561-570. doi: 10.18388/abp.2020_5418.

Abstract

Due to the lack of markers (ER, PR, and HER-2/Neu) for the molecular-targeted therapies triple-negative breast cancer (TNBC) is more challenging than other subtypes of breast cancer. Moreover, the conventional chemotherapeutic agents are still the mainstay of most therapeutic protocols and eventually turn into a refractory drug-resistance , hence, more efficient therapeutic regimens are urgently required. The present study aimed to elucidate the effects of PU-H71 combined with DHEA on triple-negative breast cancer cell line MDA-MB-231 and to assess the synergy using the Chou-Talalay method. The combined therapy controlled the expression of an array of antioxidants and metabolizing enzymes, leading to the induction of oxidative stress which in turn induced apoptotic cell death. Our results indicated that the combined treatment with PU-H71 and DHEA exerts a synergistic anti-tumor effect on MDA-MB-231 triple-negative breast cancer cell line.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Benzodioxoles / pharmacology*
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Line, Tumor
  • Dehydroepiandrosterone / pharmacology*
  • Drug Synergism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glucosephosphate Dehydrogenase / genetics
  • Glucosephosphate Dehydrogenase / metabolism
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • HSP90 Heat-Shock Proteins / genetics*
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Models, Biological
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Purines / pharmacology*
  • Triple Negative Breast Neoplasms / drug therapy

Substances

  • Benzodioxoles
  • HSP90 Heat-Shock Proteins
  • HSP90AA2P protein, human
  • Ki-67 Antigen
  • MKI67 protein, human
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Purines
  • 9H-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-N-(1-methylethyl)-
  • Dehydroepiandrosterone
  • Glucosephosphate Dehydrogenase
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Caspases