Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells
Open Access
- 2 February 2009
- journal article
- Published by Springer Science and Business Media LLC in Journal of Biomedical Science
- Vol. 16 (1), 16
- https://doi.org/10.1186/1423-0127-16-16
Abstract
Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, isolated from the traditional Chinese herb Artemisia annua, is recommended as the first-line anti-malarial drug with low toxicity. DHA has been shown to possess promising anticancer activities and induce cancer cell death through apoptotic pathways, although the molecular mechanisms are not well understood. In this study, cell counting kit (CCK-8) assay was employed to evaluate the survival of DHA-treated ASTC-a-1 cells. The induction of apoptosis was detected by Hoechst 33258 and PI staining as well as flow cytometry analysis. Collapse of mitochondrial transmembrane potential (ΔΨm) was measured by dynamic detection under a laser scanning confocal microscope and flow cytometry analysis using Rhodamine123. Caspase-3 activities measured with or without Z-VAD-fmk (a broad spectrum caspase inhibitor) pretreatment by FRET techniques, caspase-3 activity measurement, and western blotting analysis. Our results indicated that DHA induced apoptotic cell death in a dose- and time-dependent manner, which was accompanied by mitochondrial morphology changes, the loss of ΔΨm and the activation of caspase-3. These results show for the first time that DHA can inhibit proliferation and induce apoptosis via caspase-3-dependent mitochondrial death pathway in ASTC-a-1 cells. Our work may provide evidence for further studies of DHA as a possible anticancer drug in the clinical treatment of lung adenocarcinoma.Keywords
This publication has 37 references indexed in Scilit:
- Induction of Apoptosis and Inhibition of Cell Migration and Tube-Like Formation by Dihydroartemisinin in Murine Lymphatic Endothelial CellsPharmacology, 2007
- Real-time monitoring full length bid interacting with Bax during TNF-α-induced apoptosisApoptosis, 2007
- TRAIL-induced apoptosis proceeding from caspase-3-dependent and -independent pathways in distinct HeLa cellsBiochemical and Biophysical Research Communications, 2006
- Single Cell FRET Imaging for Determination of Pathway of Tumor Cell Apoptosis Induced by Photofrin-PDTCell Cycle, 2006
- Real-time detection of caspase-2 activation in a single living HeLa cell during cisplatin-induced apoptosisJournal of Biomedical Optics, 2006
- Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivoCancer Research, 2005
- Artemisinin derivatives: toxic for laboratory animals, safe for humans?Toxicology Letters, 2004
- Programmed Cell Death in Animal DevelopmentCell, 1997
- Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the ratCancer Letters, 1995
- Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death.The Journal of Experimental Medicine, 1995