Wilforol A inhibits human glioma cell proliferation and deactivates the PI3K/AKT signaling pathway.
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| Abstract | OBJECTIVES: To study the anti-proliferation activity of wilforol A against glioma cells and its possible molecular mechanisms. METHODS: Human glioma cell lines U118 MG and A172, human tracheal epithelial cells (TECs) and astrocytes (HAs) were exposed to various concentrations of wilforol A and evaluated for viability, apoptosis, and levels of proteins using WST-8 assay, flow cytometry and Western blot analysis, respectively. RESULTS:
Wilforol A inhibited the growth of U118 MG and A172 cells, but not TECs and HAs, in a concentration-dependent manner and the estimated IC50 were 6 to 11 μM after 4 h-exposure. Apoptosis was induced at an apoptotic rate of about 40% at 100 μM in U118 MG and A172 cells, but the rates were less than 3% in TECs and HAs. Co-exposure to caspase inhibitor Z-VAD-fmk significantly reduced wilforol A-induced apoptosis. Wilforol A treatment also reduced the colony formation ability of U118 MG cells and triggered a significant increase in ROS production. Elevated levels of pro-apoptotic proteins p53, Bax and cleaved caspase 3 and reduced level of the anti-apoptotic protein Bcl-2 were observed in glioma cells exposed to wilforol A. The expression of PI3K and p-Akt genes in the PI3K/AKT pathways were significantly downregulated in glioma cells treated with wilforol A. CONCLUSIONS:
Wilforol A inhibits the growth of glioma cells, reduces the levels of proteins in the P13K/Akt signal transduction pathways and increases the levels of pro-apoptotic proteins.
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| Authors | Zhihan Wang, Li Ren, Hao Xu, Zilong Wei, Hongjun Zeng |
| Journal | Acta biochimica Polonica (Acta Biochim Pol) Vol. 70 Issue 1 Pg. 123-129 (Feb 16 2023) ISSN: 1734-154X [Electronic] Poland |
| PMID | 36795994 (Publication Type: Journal Article) |
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