Verteporfin-photoinduced apoptosis in HepG2 cells mediated by reactive oxygen and nitrogen species intermediates.
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 (Deltapsi(m)) 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.
Chiou
Jeng-Fong
JF
Graduate Institute of Medical Sciences, School of Medicine, National Defense Medical Center, PO Box 90048-518, Taipei, Taiwan.
Wang
Yu-Huei
YH
Jou
Mei-Jie
MJ
Liu
Tsan-Zon
TZ
Shiau
Chia-Yang
CY
D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D056945:Hep G2 Cells; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077362:Verteporfin
D017319:Photosensitizing Agents; D011166:Porphyrins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D000077362:Verteporfin