Wilforol A inhibits human glioma cell proliferation and deactivates the PI3K/AKT signaling pathway

Zhihan   Wang; Li   Ren; Hao  Xu; Zilong  Wei; Hongjun Zeng

doi:10.18388/abp.2020_6327

Zhihan Wang Department of Neurosurgery, Pudong Hospital Affiliated to Fudan University, Shanghai, China
Li Ren Department of Neurosurgery, Pudong Hospital Affiliated to Fudan University, Shanghai, China
Hao Xu Department of Neurosurgery, Pudong Hospital Affiliated to Fudan University, Shanghai, China
Zilong Wei Department of Neurosurgery, Pudong Hospital Affiliated to Fudan University, Shanghai, China
Hongjun Zeng Department of Neurosurgery, Pudong Hospital Affiliated to Fudan University, Shanghai, China https://orcid.org/0000-0002-9109-9477

DOI: https://doi.org/10.18388/abp.2020_6327

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.