Angiotensin II receptor antagonist olmesartan and NF-kappaB inhibitor as cytotoxic and apoptotic agents in MCF-7 human cell line

J Chemother. 2016 Aug;28(4):314-20. doi: 10.1179/1973947815Y.0000000055.

Abstract

Objective: Over expression of renin-angiotensin system (RAS) and nuclear factor-kappaB (NF-kappaB) have major role in many cancers. In this study, role of angiotensin II (Ag II) and NF-kappaB pathway in breast cancer cell line (MCF-7) proliferation were studied using olmesartan (as a novel Ag II antagonist) and Bay11-7082 (as NF-kappaB inhibitor).

Materials and methods: Cells were treated with different concentrations of olmesartan and Bay11-7082.Cell proliferation was determined by 4, 5-Dimethylthiazol-2-yl, 2, 5-diphenyl tetrazolium (MTT) assay. Apoptotic cells were evaluated using PI staining of DNA fragmentation.

Results: Olmesartan and Bay11-7082 decreased cell viability. Combination of olmesartan with Bay11-7082 also decreased cell viability as compared with single agent treatments. Results showed that apoptosis is involved in olmesartan and Bay11-7082-induced toxicity.

Conclusion: Olmesartan and Bay11-7082 inhibit the MCF-7 cells growth indicating RAS and NF-kappaB pathway blockade lead to cytotoxicity and apoptosis induction against tumour cells. So ARBs and NF-kappaB pathway inhibitors could be considered as anticancer drugs in future.

Keywords: Bay11-7082; Cytotoxicity; MCF-7; Olmesartan.

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / toxicity*
  • Antineoplastic Agents / toxicity*
  • Apoptosis
  • Cell Line
  • Cell Survival / drug effects
  • Humans
  • Imidazoles / toxicity*
  • MCF-7 Cells
  • NF-kappa B / antagonists & inhibitors*
  • Nitriles / toxicity*
  • Sulfones / toxicity*
  • Tetrazoles / toxicity*

Substances

  • 3-(4-methylphenylsulfonyl)-2-propenenitrile
  • Angiotensin II Type 1 Receptor Blockers
  • Antineoplastic Agents
  • Imidazoles
  • NF-kappa B
  • Nitriles
  • Sulfones
  • Tetrazoles
  • olmesartan