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Updated: Jun 19, 2026

An In-House-Built and Light-Emitting-Diode-Based Photodynamic Therapy Device for Enhancing Verteporfin Cytotoxicity in a 2D Cell Culture Model
Published on: January 13, 2023
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.
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 (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.
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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