期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 51, 期 1, 页码 53-68出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2011.03.042
关键词
Lysosomal photodamage; NPe6-PDT; Bax; Apoptosis; Mitochondrial pathway; Free radicals
资金
- National Basic Research Program of China [2011CB910402, 2010CB732602]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT0829]
- National Natural Science Foundation of China [30870676, 30870658]
Lysosomal photosensitizers have been used in photodynamic therapy. The combination of such photosensitizers and light causes lysosomal photodamage, inducing cell death. Lysosomal disruption can lead to apoptosis but its signaling pathways remain to be elucidated. In this study, N-aspartyl chlorin e6 (NPe6), an effective photosensitizer that preferentially accumulates in lysosomes, was used to study the mechanism of apoptosis caused by lysosomal photodamage. Apoptosis in living human lung adenocarcinoma cells (ASTC-a-1) after NPe6-photodynamic treatment (NPe6-PDT) was studied using real-time single-cell analysis. Our results demonstrated that NPe6-PDT induced rapid generation of reactive oxygen species (ROS). The photodynamically produced ROS caused a rapid destruction of lysosomes, leading to release of cathepsins, and the ROS scavengers vitamin C and NAC prevent the effects. Then the following spatiotemporal sequence of cellular events was observed during cell apoptosis: Bcl-2-associated X protein (Bax) activation, cytochrome c release, and caspase-9/-3 activation. Importantly, the activation of Bax proved to be a crucial event in this apoptotic machinery, because suppressing the endogenous Bax using siRNA could significantly inhibit cytochrome c release and caspase-9/-3 activation and protect the cell from death. In conclusion, this study demonstrates that PDT with lysosomal photosensitizer induces Bax activation and subsequently initiates the mitochondrial apoptotic pathway. (C) 2011 Elsevier Inc. All rights reserved.
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