J Biomed Sci. 2009 Feb 2;16:16.
Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells.
Lu YY, Chen TS, Qu JL, Pan WL, Sun L, Wei XB.
Key Laboratory of Laser Life Science & Institute of Laser Life
Science, South China Normal University, Guangzhou 510631, PR China.
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.
METHODS: 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 (DeltaPsim) 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. RESULTS: 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 DeltaPsim and the activation of
CONCLUSION: 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.