Search

Our primary studies had shown that danthron induced cytotoxic effects, including apoptosis and inhibition of migration and invasion. However, danthron-affected DNA damage and repair gene expressions are not clear. In this study, we investigated to examine whether or not danthron induced DNA damage and inhibited DNA repair gene expression in human brain glioblastoma multiforms (GBM 8401) cells. The results from Comet assay indicated that incubation of GBM 8401 cells with 0, 50, 100 and 150 μM of danthron led to a longer DNA migration smear based on the single cell electrophoresis (Comet tail). The results from real-time PCR assay demonstrated that 100 μM of danthron for 24 h treatment in GBM 8401 cells led to decrease all examined ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR), breast cancer 1, early onset (BRCA-1), 14-3-3 proteins sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK) and O 6-methylguanine-DNA methyltransferase (MGMT) mRNA expressions. Taken together, the present study showed that danthron caused DNA damage and inhibited DNA repair genes, which may be the factors for danthron-inhibited cell growth in vitro. [ABSTRACT FROM AUTHOR]

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 (ΔΨ 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 Ca2+ 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. [ABSTRACT FROM AUTHOR]