Salidroside promotes apoptosis of human HCT116 colon cancer cells by regulating Wnt/β-catenin signaling pathway

Lijuan Cui,Yi Li,Jiao He,Yunfei Zhao,Chuan Ye,Xuan Luo,Zhengyue He,Boan Lai

doi:10.1016/j.prmcm.2022.100088

Lijuan Cui, Yi Li + Show 6 more

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https://doi.org/10.1016/j.prmcm.2022.100088

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Abstract

This study aimed to investigate the inhibitory effects of salidroside (Sal) on the proliferation and migration of human HCT116 colon cancer cell lines and the involved mechanisms. Bioinformatics and Schrodinger docking were employed to evaluate the potential targets and binding potential of Sal in the regulation of colon cancer. CCK-8 kit was employed to determine the cytotoxicity of Sal in various concentrations on HCT116 cells. The proliferation and migration were evaluated by scratch adhesion and transwell assays, respectively. The apoptosis was analyzed by flow cytometric assay. Apoptosis-related proteins Bax, Bcl-2, Cyto-c and cleaved caspase-3/7/9 were further detected by western blot analysis. The genes and proteins expression of Wnt-5b/9a, secreted frizzled-related protein 4/5 (SFRP 4/5), dishevelled 2 (DVL2), ras-related C3 botulinum toxin substrate 1 (RAC1) and β-catenin were detected by western blot, immunofluorescence and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) techniques. Bioinformatics and docking results showed that Sal could regulate the Wnt signaling pathway and had binding potential with β-catenin (-8.150), DVL2 (-7.897) and Rac1 (-8.824). Sal at a concentration of 0.5-16 µM tended to inhibit the viability of human HCT116 cells, especially in a concentration-dependent manner after 48 h incubation. And it could notably inhibit the proliferation and migration of HCT116 cells. Increased apoptosis was demonstrated by flow cytometry analysis after Sal intervention. Parallelly, Sal intervention significantly increased proapoptotic proteins Bax, Cyto-c and cleaved caspase-3/7/9, while restricted the expression of anti-apoptotic protein Bcl-2. Further analyses revealed that Sal could suppress the proteins and genes expression of Wnt-5b/9a, SFRP 4/5, DVL2, RAC1 and β-catenin. Sal could inhibit the proliferation and migration of HCT116 cells, as well trigger its apoptosis. The involved mechanism maybe related to the regulation of Wnt/β-catenin signaling pathway.

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