Isoliquiritigenin inhibits the proliferation and induces the differentiation of human glioma stem cells.

Abstract

Glioma stem cells (GSCs) have been proven to be resistant to various therapeutic strategies, such as temozolomide chemotherapy and radiotherapy, leading to glioma recurrence. Isoliquiritigenin (ISL), a menber of the flavonoids isolated from liquorice has been found to be a potent stimulator of cell differentiation and has potential application for treating various types of cancer including human brain glioma. However, the antitumor activity of ISL on GSCs and the signaling pathway underlying its therapeutic effects are poorly understood. In the present study, GSCs were isolated from SHG44 human glioma cells by serum-free culture and treated with ISL or DAPT (a Notch/γ-secretase inhibitor). It was found that ISL dose-dependently inhibited GSC growth after 72 h of treatment and decreased the formation of tumor spheres. Meanwhile, GSCs differentiated into astrocytes and neurons. Furthermore, these therapeutic effects were accompanied by downregulation of Notch1 and Hes1 at the protein and mRNA levels. Taken together, our results demonstrated that ISL exhibits antitumor effects on GSCs by inhibiting proliferation and inducing differentiation. The therapeutic effect may be related to downregulation of the Notch1 signaling pathway. Application of ISL presents potential benefits for the treatment of human brain glioma.