Tanshinone IIA inhibits the growth, attenuates the stemness and induces the apoptosis of human glioma stem cells

Abstract

Glioma stem cells (GSCs) are believed to contribute to glioblastoma multiforme (GBM) propagation and treatment resistance. Tanshinone IIA possesses anticancer and anti-inflammatory activities. This study aimed to determine the inhibitory effect of tanshinone IIA on human GSCs in vitro and in vivo and to explore the underlying mechanisms. In the present study, human GBM neurospheres (GBMS) were isolated from adherent GBM cells in serum-free medium, and the cells from the GBMS displayed characteristics of GSCs. Results from the MTT, neurosphere formation and in vivo inhibition assays revealed that tanshinone IIA had a significant inhibitory effect on human GSCs in vitro and in vivo. Furthermore, tanshinone IIA increased the expression of differentiation and neural lineage markers including GFAP and β-tubulin, decreased expression of GSC markers including CD133 and nestin, and induced GSC apoptosis in vitro and in vivo in a dose-dependent manner. Inflammatory cytokines and signaling pathways are believed to play key roles in maintaining the stem-like properties in human glioma cells. In the present study, inflammatory cytokine interleukin 6 (IL6) and its downstream activated signal transducer and activator of transcription 3 [phospho-STAT3(tyrosine705) and phospho-STAT3(serine727)] were downregulated after tanshinone IIA treatment in vitro and in vivo. This result indicated that disturbance of the IL6/STAT3 signaling axis by tanshinone IIA is closely related to the growth inhibition of GSCs. Taken together, our results indicate that tanshinone IIA has the potential to target and kill GSCs through suppression of proliferation, attenuation of stemness and induction of apoptosis. Its mechanism of activity may be associated with attenuation of the IL6/STAT3 signaling pathway.