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A Novel Sphingosine Kinase 1 Inhibitor (SKI-5C) Induces Cell Death of Wilms' Tumor Cells

A Novel Sphingosine Kinase 1 Inhibitor (SKI-5C) Induces Cell Death of Wilms' Tumor Cells

Zhi-Heng Li, Yan-Fang Tao, Li-Xiao Xu, He Zhao, Xiao-Lu Li, Fang Fang, Yi Wu, Jun Lu, Yan-Hong Li, Wei-Wei Du, Jun-Li Ren, Yi-Ping Li, Yun-Yun Xu, Xing Feng, Jian Wang, Wei-Qi He, Jian Pan

Am J Transl Res. 2016 Nov 15;8(11):4548-4563.

PMID: 27904661

Abstract:

Sphingosine kinase 1 (SphK1) is over-expressed in many cancers and therefore serves as a biomarker for cancer prognosis. SKI-5C is a new SphK1 inhibitor, and until now its molecular function in Wilms' tumor cells remained unknown. Here, using CCK-8 and nude mice experiments we assessed cell growth in Wilms' tumor cell lines (SK-NEP-1 and G401) in vitro and in vivo. We demonstrated that SphK1 is highly expressed in SK-NEP-1 and G401 cells, and through annexin V/propidium iodide staining and flow cytometry analysis, we detected cell apoptosis. Treatment with SKI-5C inhibited proliferation and induced apoptosis of SK-NEP-1 and G401 cells in a dose-dependent manner. Moreover, SKI-5C treatment inhibited the growth of SK-NEP-1 xenograft tumors in nude mice, with few side effects. Our microarray analysis revealed that SKI-5C-treated SK-NEP-1 cells mostly downregulated PRKACA and significantly inhibited phosphorylation of ERK1/2 and NF-κB p65. These results imply that SKI-5C induces apoptosis of SK-NEP-1 cells through the PRKACA/MAPK/NF-κB pathway. While, further research is required to determine the underlying details, these results provide new clues for the molecular mechanism of cell death induced by SKI-5C and suggest that SKI-5C may act as new candidate drug for Wilms' tumor.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP120005552	SKI 5C		120005-55-2	Price

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