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Up-regulation of P-glycoprotein expression by catalase via JNK activation in HepG2 cells

Lin Li1, Jianfeng Xu, Taishan Min

  • 1Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, China.

Redox Report : Communications in Free Radical Research
|September 21, 2006
PubMed

Insights

Antioxidants like catalase and N-acetylcysteine surprisingly increased multidrug resistance (MDR) gene expression in HepG2 cells. This suggests a complex role for antioxidants in cancer treatment, potentially involving reactive oxygen species (ROS) and JNK signaling.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Multidrug resistance (MDR) is a significant challenge in cancer therapy, often linked to MDR1 gene overexpression.
  • Antioxidants have been investigated for their potential to down-regulate MDR1 expression as a cancer treatment strategy.

Purpose of the Study:

  • To investigate the effects of catalase and N-acetylcysteine (NAC) on intrinsic MDR1 overexpression in HepG2 cells.
  • To elucidate the role of reactive oxygen species (ROS) and JNK signaling in antioxidant-mediated MDR1 regulation.

Main Methods:

  • HepG2 cells were treated with catalase or NAC.
  • MDR1 mRNA levels and P-glycoprotein activity were measured.
  • Intracellular ROS levels were assessed.
  • The effect of a JNK inhibitor (SP600125) was evaluated.
  • Experiments were conducted in parallel with other cell lines (MCF-7, A549, A431).

Main Results:

  • Catalase and NAC treatments significantly increased MDR1 mRNA and P-glycoprotein activity in HepG2 cells.
  • A reduction in intracellular ROS was observed following antioxidant treatment.
  • The JNK inhibitor SP600125 dose-dependently abolished the positive effect of catalase on drug transporter activity.
  • The up-regulation of P-glycoprotein by catalase was specific to HepG2 cells.

Conclusions:

  • Catalase up-regulates P-glycoprotein expression in HepG2 cells, potentially by reducing intracellular ROS.
  • The JNK signaling pathway appears to mediate this catalase-induced up-regulation.
  • These findings suggest a complex, cell-specific interaction between antioxidants, ROS, and MDR1 expression.

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