Glioblastoma multiforme (GBM) is an extremely aggressive and devastating malignant
tumor in the central nervous system. Its incidence is increasing and the prognosis is poor.
Artocarpin is a natural prenylated
flavonoid with various anti-inflammatory and anti-
tumor properties. Studies have shown that
artocarpin is associated with cell death of primary
glioblastoma cells. However, the in vivo effects and the cellular and molecular mechanisms modulating the anticancer activities of
artocarpin remain unknown. In this study, we demonstrated that treating the
glioblastoma cell lines U87 and U118 cells with
artocarpin induced apoptosis.
Artocarpin-induced apoptosis is associated with
caspase activation and
poly (ADP-ribose) polymerase (PARP) cleavage and is mediated by the mitochondrial pathway. This is associated with mitochondrial depolarization, mitochondrial-derived reactive oxidative species (ROS) production,
cytochrome c release, Bad and Bax upregulations, and Bcl-2 downregulation.
Artocarpin induced
NADPH oxidase/ROS generation plays an important role in the mitochondrial pathway activation. Furthermore, we found
artocarpin-induced ROS production in mitochondria is associated with Akt- and ERK1/2 activation.
After treatment with
artocarpin, ROS causes PI3K/Akt/ERK1/2-induced cell death of these
tumor cells. These observations were further verified by the results from the implantation of both U87 and U118 cells into in vivo mouse. In conclusion, our findings suggest that
artocarpin induces mitochondria-associated apoptosis of
glioma cells, suggesting that artocarpine can be a potential chemotherapeutic agent for future GBM treatment.