Anticarin β Inhibits Human Glioma Progression by Suppressing Cancer Stemness via STAT3

Glioma is the most common form of malignant brain cancer. It is very difficult to cure malignant glioma because of the presence of glioma stem cells, which are a barrier to cure, have high tumorigenesis, associated with drug resistance, and responsible for relapse by regulating stemness genes. In this study, our results demonstrated that anticarin β, a natural compound from Antiaris toxicaria, can effectively and selectively suppress proliferation and cause apoptosis in glioma cells, which has an IC(50) that is 100 times lower than that in mouse normal neural stem cells. Importantly, cell sphere formation assay and real time-quantitative analysis reveal that anticarin β inhibits cancer stemness by modulating related stemness gene expression. Additionally, anticarin β induces DNA damage to regulate the oncogene expression of signal transducer and activator of transcription 3 (STAT3), Akt, mitogen-activated protein kinases (MAPKs), and eventually leading to apoptosis. Furthermore, anticarin β effectively inhibits glioma growth and prolongs the lifts pan of tumor-bearing mice without systemic toxicity in the orthotopic xenograft mice model. These results suggest that anticarin β is a promising candidate inhibitor for malignant glioma.