Sesamol induces mitochondrial apoptosis pathway in HCT116 human colon cancer cells via pro-oxidant effect

Life Sci. 2016 Aug 1;158:46-56. doi: 10.1016/j.lfs.2016.06.017. Epub 2016 Jun 17.

Abstract

Aims: Sesamol lignan is a phenolic compound found in sesame seeds. We investigated the effect of different concentrations of sesamol on oxidative stress in colorectal carcinoma cells (HCT116).

Main methods: Antioxidation in vitro was determined from elimination of the DPPH radical, ferric reducing-antioxidant power (FRAP), O2(-), and peroxyl radical scavenging activity. Intracellular O2(-), H2O2 and GSH levels were determined by DHE, DCFH-DA, and CMF-DA assay, respectively. Cell viability was detected by neutral red assay. Cell cycle proportion and mode of apoptotic HCT116 cells death was analyzed by flow cytometry. Apoptosis in sesamol-treated HCT116 cells was confirmed by morphological changes in the nuclei using DAPI staining and changes in mitochondrial membrane potential using the DiOC6(3) assay.

Key findings: Sesamol at both low (0.05 and 0.25mM) and high (0.5, 2, 5, and 10mM) concentrations concurrently reduced FRAP reagent and scavenged DPPH, and O2(-). Sesamol at low concentrations scavenged ROO, but ROO-scavenging was decreased at higher concentrations. Sesamol suppressed cell viability via disruption of cell cycle progression at high concentrations (0.5, 1, 2, and 5mM), thereby causing S-phase arrest and inducing apoptosis-through the production of intracellular O2(-), mitochondrial dysfunction, and DNA fragmentation.

Significance: High concentrations of sesamol induced the mitochondrial apoptosis pathway in human colon cancer HCT116 cells via a pro-oxidant effect.

Keywords: Apoptosis; Chemopreventive effect; Human colon cell line; Reactive oxygen species; Sesame; Sesamol.

MeSH terms

  • Apoptosis / drug effects*
  • Benzodioxoles / pharmacology*
  • Cell Cycle / drug effects
  • Colonic Neoplasms / pathology*
  • HCT116 Cells
  • Humans
  • Mitochondria / drug effects*
  • Phenols / pharmacology*
  • Reactive Oxygen Species / pharmacology*

Substances

  • Benzodioxoles
  • Phenols
  • Reactive Oxygen Species
  • sesamol