The role of ROS and NF-κB pathway in olmesartan induced-toxicity in HeLa and mcf-7 cell lines

Biomed Pharmacother. 2017 Sep;93:429-434. doi: 10.1016/j.biopha.2017.06.074. Epub 2017 Jun 27.

Abstract

We have recently shown that olmesartan could induce toxicity in HeLa and MCF-7 cell lines. In this study we investigated toxicity mechanism of olmesartan in HeLa and MCF-7 cell lines. HeLa and MCF-7 cells were cultured in DMEM in optimum conditions. Cells were pretreated with rutin as an antioxidant and treated with olmesartan as a cytotoxic agent. Cell proliferation was determined by MTT assay. The role of ROS was determined using DCFH-DA by flow cytometry analysis. Also, cells were treated with olmesartan (5mM) and Bay 11-7-82 (25μM) for 24h, then expression of apoptotic proteins including Bax, caspase3 and IκB were investigated in both cell lines by western blotting. Cell viability decreased with olmesartan in malignant cell lines. Kinetic of ROS assay showed increment of ROS generation starting at 2h which peaked at 4h after treatment. Pretreatment with antioxidant rutin decreased ROS increment which was consistent with improved viability of olmesartan-treated cells. Apoptosis results showed that olmesartan and Bay 11-7082 increased expression of apoptotic proteins such as Bax, caspase3 and IκB. Results proposed ROS increment and apoptosis could be involving mechanisms in olmesartan-induced toxicity in HeLa and MCF-7 cell lines.

Keywords: Antioxidant; Apoptosis; HeLa; MCF-7; Olmesartan; ROS; Rutin.

MeSH terms

  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • HeLa Cells
  • Humans
  • Imidazoles / toxicity*
  • Intracellular Space / metabolism
  • MCF-7 Cells
  • NF-kappa B / metabolism*
  • Nitriles / pharmacology
  • Protective Agents / pharmacology
  • Reactive Oxygen Species / metabolism*
  • Rutin / pharmacology
  • Signal Transduction / drug effects*
  • Sulfones / pharmacology
  • Tetrazoles / toxicity*

Substances

  • 3-(4-methylphenylsulfonyl)-2-propenenitrile
  • Imidazoles
  • NF-kappa B
  • Nitriles
  • Protective Agents
  • Reactive Oxygen Species
  • Sulfones
  • Tetrazoles
  • Rutin
  • olmesartan