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

Jeng Fong Chiou, Yu Huei Wang, Mei Jie Jou, Tsan Zon Liu, Chia Yang Shiau

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Photodynamic therapy (PDT) is a rapidly evolving treatment modality with diverse usages in the field of cancer therapy. Most of PDT is based on free radical-mediated photo-killing of cancer cells. This study aimed to elucidate the detailed cascade of events that lead to apoptotic cell death of HepG2 cells resulting from the photodynamic effect (PDE) of verteporfin. PDE of verteporfin could rapidly provoke hyper-oxidative stress and caspase activity. Glutathione (GSH) depletion and lipid peroxidation phenomena could simultaneously be evoked. The membrane integrity was decreased and permeability as reflected by the depolarization of the mitochondrial membrane potential (Δψm) increased, resulting in a sudden influx of cytosolic calcium into the mitochondria. Altogether, it is suggested that these events serve as the final arbitrator to initiate the lethal apoptotic process of HepG2 cells under PDE. In addition, the data are consistent with the notion that GSH depletion is an effective strategy to sensitize cancer cells to undergo apoptosis.

Original languageEnglish
Pages (from-to)155-170
Number of pages16
JournalFree Radical Research
Volume44
Issue number2
DOIs
Publication statusPublished - 2010

Keywords

  • Apoptosis
  • Benzoporphyrin monoacid ring A
  • Free radicals
  • Glutathione depletion; lipid peroxidation
  • Mitochondrial calcium overload
  • Photodynamic therapy

ASJC Scopus subject areas

  • Biochemistry

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