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Olaquindox induces apoptosis through the mitochondrial pathway in HepG2 cells

Jiajie Zou1, Qian Chen, Xi Jin

  • 1Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, PR China.

Toxicology
|May 10, 2011
PubMed

Insights

Olaquindox causes S-phase cell cycle arrest and apoptosis in HepG2 cells. This involves oxidative stress, DNA damage, and mitochondrial pathway activation, including caspase-3 and caspase-9.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Cell Biology

Background:

  • Olaquindox is a feed additive used for growth promotion in pigs.
  • Previous studies showed olaquindox induces DNA damage and oxidative stress in HepG2 cells.

Purpose of the Study:

  • To investigate the molecular mechanisms of cell cycle arrest and apoptosis induced by olaquindox in HepG2 cells.

Main Methods:

  • Cell cycle analysis (sub-G1 population, S-phase arrest)
  • Apoptosis assays (nuclear condensation, DNA fragmentation)
  • Mitochondrial function assessment (Δψ(m), mPTP opening)
  • Protein expression analysis (caspases, PARP, Bcl-2, Bax, p53)
  • Reactive oxygen species (ROS) detection
  • Cytochrome c release assay

Main Results:

  • Olaquindox induced S-phase cell cycle arrest and dose-dependent apoptosis in HepG2 cells.
  • Apoptosis was mediated by ROS, involving mitochondrial DNA damage, nuclear DNA damage, mitochondrial membrane potential collapse, and mPTP opening.
  • Key molecular events included p53 upregulation, altered Bcl-2 family protein expression (downregulation of Bcl-2, upregulation of Bax), and cytochrome c release.

Conclusions:

  • Olaquindox triggers apoptosis in HepG2 cells via a mitochondrial pathway dependent on caspase-9 and caspase-3.
  • This process is associated with p53 activation, modulation of Bcl-2 family proteins, mitochondrial membrane potential disruption, and mPTP opening.

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