Affiliations: MOE Key Laboratory of Laser Life Science and Institute
of Laser Life Science, College of Biophotonics, South China Normal University,
Guangzhou, Guangdong, China
Abstract: Photofrin-mediated photodynamic therapy (PF-PDT) can induce cell
apoptosis via the mitochondria/caspase-3 pathway. Here, we further investigate
the mechanism involved in the mitochondrial apoptotic process induced by
PF-PDT. A high-level intracellular reactive oxygen species (ROS) generation in
mitochondria, mitochondrial swelling, and dissipation of mitochondrial
transmembrane potential were observed immediately after irradiation, indicating
that mitochondria were the major ROS generation sites and also the first
oxidative damage sites after PF-PDT treatment. For mitochondrial permeability
detection, the decrease of calcein fluorescence emission intensity and release
of cytochrome c were observed immediately after PF-PDT treatment, indicating
the occurrence of mitochondrial inner membrane permeabilization (MIMP) and the
mitochondrial outer membrane permeabilization (MOMP). However, cytochrome c
release was not prevented by cyclosporine (CsA), a specific inhibitor of
mitochondrial permeability transition (MPT). Taken together, these results
demonstrated that PF-PDT caused simultaneous onset of MIMP and MOMP immediately
after the treatment, and MOMP was independent of the MPT. Besides, inducible
mitochondrial ROS generation played key roles in PF-PDT-induced cell apoptosis.
This study will be benefit for understanding the mechanism involved in the
initial mitochondrial oxidative damage by PF-PDT.
Keywords: Photofrin, photodynamic therapy, mitochondria, reactive oxygen species
