Mitochondria-dependent apoptosis induced by a novel amphipathic photochemotherapeutic agent ZnPcS2P2 in HL60 cells

• 来源期刊: 中国药理学报（英文版）
• 关键词: photodynamic therapy zinc phthalocyanine apoptosis cytochrome c caspases HL60 cells
• 年，卷（期）: 2005,（9）
• 页码范围: 1138-1144
• 页数: 7页
• 语种: 英文

摘要

Aim: To investigate the mechanism underlying the killing effects of a novel amphipathic photosensitizer, disulfonated diphthalimidomethyl phthalocyanine zinc (ZnPcS2P2), mediated photodynamic therapy (ZnPc-PDT) in human myelogenous leukemia HL60 cells. Methods: After incubation for 5 h with 0.5 μmol/L ZnPcS2P2, the HL60 cells were exposed to a light source of 670 nm wavelength.Thereafter, the cells were detected at different time intervals after PDT. The characteristics of apoptosis were detected by observation of ultrastructure assay,DNA fragmentation assay and terminal deoxynucleotidyl transferase deoxyuridine nick-end labeling method (TUNEL). Mitochondria-dependent apoptosis was determined by the detection of mitochondrial membrane potential (Δψm), activities of caspase family protease and of caspase-3, cytosol cytochrome c. Proteins Bcl-2and Bax were detected by immunoblot analysis. Results: Evident characteristics of apoptosis were observed post-ZnPc-PDT with ultrastructure assay, DNA fragmentation assay and TUNEL staining. TUNEL assay showed that apoptotic rates in the cells collected from 6 h, 12 h and 24 h after PDT were 9.6%, 24.4%, and 33.0%,respectively. HL60 cells underwent mitochondria-dependent apoptosis as a result of cytochrome c release from mitochondria into cytosol accompanied by a reduction of Δψm. The activities of caspase family protease and of caspase-3were elevated. Furthermore, ZnPc-PDT could remarkably down-regulate the Bcl-2pro-apoptotic protein and up-regulate the anti-apoptotic Bax protein. Conclusion:ZnPc-PDT could induce mitochondria-dependent apoptosis in HL60 cells.