Low concentrations of cylindrospermopsin induce increases of reactive oxygen species levels, metabolism and proliferation in human hepatoma cells (HepG2)

Toxicol In Vitro. 2015 Apr;29(3):479-88. doi: 10.1016/j.tiv.2014.12.022. Epub 2015 Jan 6.

Abstract

Human hepatoma cells (HepG2) were exposed to purified cylindrospermopsin (CYN), a potent toxicant for eukaryotic cells produced by several cyanobacteria. CYN was not toxic at concentrations up to 10 μgl(-1), leading to increased viability and metabolism in cells cultured with 10% fetal bovine serum (FBS). Reduction of FBS concentration to 2% and induction of cytochrome P450 (CYP) isoforms were performed in order to make xenobiotic-metabolizing capacity of HepG2 cells closest to that of 'normal' cells. HepG2 cells proliferated less after CYPs-induction, and this induction has lead to similar results of non-induced cells, except for few individual parameters such lipid peroxidation. Foremost, low concentrations of CYN (below or equal 10 μgl(-1)) have induced HepG2 cells proliferation and metabolism increase, which was not expected.

Keywords: CYPs; Cell lineage; Cyanotoxin; Cylindrospermopsin; HepG2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids
  • Bacterial Toxins
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation / drug effects*
  • Cell Survival
  • Cyanobacteria Toxins
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Hep G2 Cells
  • Humans
  • Lipid Peroxidation / drug effects
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism*
  • Uracil / analogs & derivatives*
  • Uracil / toxicity
  • Xenobiotics / metabolism

Substances

  • Alkaloids
  • Bacterial Toxins
  • Cyanobacteria Toxins
  • Reactive Oxygen Species
  • Xenobiotics
  • cylindrospermopsin
  • Uracil
  • Cytochrome P-450 Enzyme System