Curcumin Suppresses Malignant Glioma Cells Growth and Induces Apoptosis by Inhibition of SHH/ GLI1 Signaling Pathway in Vitro and Vivo.

Aims To study the role of curcumin on glioma cells via the SHH/ GLI1 pathway in vitro and vivo. Methods The effects of curcumin on proliferation, migration, apoptosis, SHH/ GLI1 signaling, and GLI1 target genes expression were evaluated in multiple glioma cell lines in vitro. A U87-implanted nude mice model was used to study the role of curcumin on tumor volume and the suppression efficacy of GLI1. Results Curcumin showed cytotoxic effects on glioma cell lines in vitro. Both mRNA and protein levels of SHH/ GLI1 signaling ( Shh, Smo, GLI1) were downregulated in a dose- and time-dependent manner. Several GLI1-dependent target genes ( Cyclin D1, Bcl-2, Foxm1) were also downregulated. Curcumin treatment prevented GLI1 translocating into the cell nucleus and reduced the concentration of its reporter. Curcumin suppressed cell proliferation, colony formation, migration, and induced apoptosis which was mediated partly through the mitochondrial pathway after an increase in the ratio of Bax to Bcl2. Intraperitoneal injection of curcumin in vivo reduced tumor volume, GLI1 expression, the number of positively stained cells, and prolonged the survival period compared with the control group. Conclusion This study shows that curcumin holds a great promise for SHH/ GLI1 targeted therapy against gliomas. [ABSTRACT FROM AUTHOR]