Verteporfin-photoinduced apoptosis in HepG2 cells mediated by reactive oxygen and nitrogen species intermediates

Jeng-Fong Chiou1, Yu-Huei Wang, Mei-Jie Jou

  • 1Graduate Institute of Medical Sciences, School of Medicine, National Defense Medical Center, PO Box 90048-518, Taipei, Taiwan.

Free Radical Research
|November 6, 2009
PubMed

Insights

Photodynamic therapy using verteporfin induces cancer cell death by creating oxidative stress and triggering apoptosis. Glutathione depletion enhances this cell-killing effect, sensitizing cancer cells to treatment.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Photodynamic therapy (PDT) is a cancer treatment utilizing light-activated drugs to generate cell-killing free radicals.
  • Understanding the precise molecular mechanisms of PDT is crucial for optimizing its efficacy.

Purpose of the Study:

  • To investigate the specific cellular events leading to apoptosis in HepG2 liver cancer cells upon exposure to verteporfin-mediated photodynamic effect (PDE).
  • To explore the role of oxidative stress and glutathione depletion in PDT-induced cell death.

Main Methods:

  • HepG2 cells were treated with verteporfin and exposed to light to induce PDE.
  • Assessed oxidative stress markers, caspase activity, glutathione (GSH) levels, lipid peroxidation, and mitochondrial membrane potential (Δψm).

Main Results:

  • Verteporfin PDE rapidly induced hyper-oxidative stress and increased caspase activity in HepG2 cells.
  • Simultaneous GSH depletion and lipid peroxidation were observed, alongside decreased membrane integrity.
  • Mitochondrial membrane potential depolarization led to calcium influx, initiating apoptosis.

Conclusions:

  • The study elucidates a cascade of events, including oxidative stress and mitochondrial dysfunction, culminating in apoptosis of HepG2 cells via verteporfin PDE.
  • Glutathione depletion emerges as a viable strategy to sensitize cancer cells to PDT-induced apoptosis.

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