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Curcumin Suppresses Malignant Glioma Cells Growth and Induces Apoptosis by Inhibition of SHH / GLI 1 Signaling Pathway in Vitro and Vivo

2013; Wiley; Volume: 19; Issue: 12 Linguagem: Inglês

10.1111/cns.12163

1755-5949

Wenzhong Du, Feng Yan, Xiaofeng Wang, Xing‐Yin Piao, Yuqiong Cui, Lingchao Chen, Xu‐Hui Lei, Xu Sun, Xing Liu, Han‐Bing Wang, Xianfeng Li, Dongbo Yang, Ying Sun, Zhefeng Zhao, Tao Jiang, Yongli Li, Chuanlu Jiang,

Retinoids in leukemia and cellular processes

Summary Aims To study the role of curcumin on glioma cells via the SHH / GLI 1 pathway in vitro and vivo . Methods The effects of curcumin on proliferation, migration, apoptosis, SHH / GLI 1 signaling, and GLI 1 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 GLI 1. Results Curcumin showed cytotoxic effects on glioma cell lines in vitro . Both mRNA and protein levels of SHH / GLI 1 signaling ( S hh, S mo, GLI 1) were downregulated in a dose‐ and time‐dependent manner. Several GLI 1‐dependent target genes ( C yclin D 1, B cl‐2, F oxm1) were also downregulated. Curcumin treatment prevented GLI 1 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 B ax to B cl2. Intraperitoneal injection of curcumin in vivo reduced tumor volume, GLI 1 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 / GLI 1 targeted therapy against gliomas.