Cordycepin induces apoptotic cell death of human brain cancer through the modulation of autophagy.

Brain cancer, in particular neuroblastoma and glioblastoma, is a global challenge to human health. Cordycepin, extracted from Cordyceps ssp., has been revealed as a strong anticancer agent through several ways; however, the mechanism, by which cordycepin counteracts brain cancers, is still poorly understood. In this study, the underlying mechanisms of cordycepin against human brain cancer cells were explored. SH-SY5Y and U251 cells were being a model to represent human neuroblastoma and glioblastoma, respectively. Here, it was found that cordycepin inhibited cell growth, and induced apoptosis in a dose-dependent manner in both SH-SY5Y and U-251 cell lines. The expression of pro-apoptotic genes, including P53, BAX, Caspase-3, and Caspase-9, were upregulated, whereas the expression of anti-apoptotic gene, BCL-2, was suppressed. Besides, cordycepin induced the generation of reactive oxygen species (ROS) along with the suppression of antioxidant genes, including GPX, SOD, and Catalase. Importantly, cordycepin was shown to involve in the activation of autophagy, which was evidenced by the increment of LC3I/II. The combination of cordycepin with chloroquine, an autophagy inhibitor, further inhibited the growth, and enhanced the death of brain cancer cells. Altogether, this finding suggested that cordycepin induced apoptosis of human brain cancer cells through mitochondrial-mediated intrinsic pathway and the modulation of autophagy. Therefore, cordycepin could be a promising candidate for the development of anticancer drugs targeting human brain cancers.