Journal
JOURNAL OF BIOMEDICAL OPTICS
Volume 15, Issue 4, Pages -Publisher
SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
DOI: 10.1117/1.3481141
Keywords
dihydroartemisinin; reactive oxygen species; apoptosis; confocal imaging; fluorescence resonance energy transfer; fluorescence recovery after photobleaching; caspases; Bcl-2 family proteins
Funding
- Program for Changjiang Scholars and Innovative Research Team in University [IRT0829]
- National Natural Science Foundation of China [30670507]
- Natural Science Foundation of Guangdong Province [8151063101000031, 9251063101000009]
Ask authors/readers for more resources
Dihydroartemisinin (DHA), a front-line antimalarial herbal compound, has been shown to possess promising anticancer activity with low toxicity. We have previously reported that DHA induced caspase-3-dependent apoptosis in human lung adenocarcinoma cells. However, the cellular target and molecular mechanism of DHA-induced apoptosis is still poorly defined. We use confocal fluorescence microscopy imaging, fluorescence resonance energy transfer, and fluorescence recovery after photobleaching techniques to explore the roles of DHA-elicited reactive oxygen species (ROS) in the DHA-induced Bcl-2 family proteins activation, mitochondrial dysfunction, caspase cascade, and cell death. Cell Counting Kit-8 assay and flow cytometry analysis showed that DHA induced ROS-mediated apoptosis. Confocal imaging analysis in a single living cell and Western blot assay showed that DHA triggered ROS-dependent Bax translocation, mitochondrial membrane depolarization, alteration of mitochondrial morphology, cytochrome c release, caspase-9, caspase-8, and caspase-3 activation, indicating the coexistence of ROS-mediated mitochondrial and death receptor pathway. Collectively, our findings demonstrate for the first time that DHA induces cell apoptosis by triggering ROS-mediated caspase-8/Bid activation and the mitochondrial pathway, which provides some novel insights into the application of DHA as a potential anticancer drug and a new therapeutic strategy by targeting ROS signaling in lung adenocarcinoma therapy in the future. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3481141]
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available