ZnPcS2P2-based photodynamic therapy induces mitochondria-dependent apoptosis in K562 cells.
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 (deltapsim) 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).
Huang
Hui-Fang
HF
Fujian Institute of Hematology, Union Hospital, Fujian Medical University, Fuzhou 350001, China.
Chen
Yuan-Zhong
YZ
Wu
Yong
Y
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D045304:Cytochromes c / Q000096:biosynthesis; D053938:DNA Fragmentation; D015536:Down-Regulation; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis; D006801:Humans; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000627:therapeutic use*; D007425:Intracellular Membranes; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009942:Organometallic Compounds / Q000627:therapeutic use*; D010778:Photochemotherapy / Q000379:methods*
D007211:Indoles; D009942:Organometallic Compounds; C064329:zinc phthalocyanine disulfonate; D045304:Cytochromes c; D016044:Fusion Proteins, bcr-abl; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases