Danthron (1,8-dihydroxyanthraquinone), is one of component from Rheum palmatum L. (Polygonaceae), has been shown several
biological activities but did not show to induce apoptosis in human
brain tumor cells. The aim of this study is to investigate the mechanisms by
danthron for the induction of apoptotic potential on human brain
glioblastoma multiforms GBM 8401 cell line.
Danthron showed a marked concentration- and time-dependent inhibition of GBM 8401 cell viability and induced apoptosis in a dose-and time-dependent manner. There was an attenuation of mitochondrial membrane potential (DeltaPsi(m)) with the alterations of Bcl-2/
Bax protein ratio in GBM 8401 cells, indicating the participation of a mitochondria-related mechanism. Pretreatment of a
caspase-8 inhibitor (
Z-IETD-FMK),
caspase-9 inhibitor (
Z-LEHD-FMK) and
caspase-3 inhibitor (Z-DEVE-FMK) significantly increased the viable of GBM 8401 cells implied that the participations of
caspases. Western blotting analysis also showed the activation of initiator
caspase-8 and
caspase-9, and executor
caspase-3 in GBM 8401 cells. Meanwhile,
danthron also promoted the generation of
reactive oxygen species (ROS) and cytosolic Ca(2+) in GBM 8401 cells. Taken together, our data showed that
danthron induced apoptosis in GBM 8401 cells through mitochondria-related and
caspase-related pathways, and it may be further evaluated as a chemotherapeutic agent for human
brain cancer.