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Acta
Biochim Biophys Sin 2005,37:488-494
doi:10.1111/j.1745-7270.2005.00067.x
ZnPcS2P2-based Photodynamic
Therapy Induces Mitochondria-dependent Apoptosis in K562 Cells
Hui-Fang HUANG, Yuan-Zhong CHEN*, and Yong WU
Fujian Institute of Hematology, Union Hospital, Fujian Medical University,
Fuzhou 350001, China
Abstract Mitochondria play a key role in the regulation of apoptosis
induced by numerous antitumor chemotherapeutic and other toxic agents.
Photodynamic therapy (PDT) exerts significant cellular killing efficacy
through either an apoptotic or necrotic cell death pathway. This study
investigated the mechanism underlying the killing effects of a novel
amphipathic photosensitizer [di-sulfonated di-phthalimidomethyl
phthalocyanine zinc (ZnPcS2P2)]-mediated
photodynamic therapy (ZnPcS2P2-PDT)
on K562 cells. Apoptosis was evident in the post-PDT cells through the
TdT-mediated dUTP nick end labeling (TUNEL) method and DNA fragmentation
assay. After ZnPcS2P2-PDT, K562 cells
underwent mitochondria-dependent apoptosis as evidenced by the release of
cytochrome c from mitochondria into cytosol, accompanied by mitochondrial
membrane potential (Dym) reduction, indicating the opening of the mitochondrial
permeability transition pore (PTP). The activities of protease from the
caspase family and caspase-3 were also significantly elevated. Furthermore,
ZnPcS2P2-PDT down-regulated the expression of
chimaeric Bcr-Abl oncoprotein, which is the molecular hallmark of chronic
myelogenous leukemia (CML).
Key words photodynamic therapy; zinc phthalocyanine; apoptosis;
mitochondria; K562 cell
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