<em>Paris</em> saponin H inhibits the proliferation of glioma cells through the A1 and A3 adenosine receptor‑mediated pathway

Bi,Linlin; Liu,Yang; Yang,Qian; Zhou,Xuanxuan; Li,Hua; Liu,Yang; Li,Jie; Lu,Yunyang; Tang,Haifeng

doi:10.3892/ijmm.2021.4863

Paris saponin H inhibits the proliferation of glioma cells through the A1 and A3 adenosine receptor‑mediated pathway

Authors:
- Linlin Bi
- Yang Liu
- Qian Yang
- Xuanxuan Zhou
- Hua Li
- Jie Li
- Yunyang Lu
- Haifeng Tang
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Affiliations: Department of Chinese Materia Medica and Natural Medicines, Air Force Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: February 1, 2021 https://doi.org/10.3892/ijmm.2021.4863
Article Number: 30
Copyright: © Bi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Paris saponin H (PSH) is a type of steroid saponin derived from Rhizoma Paridis (RP; the rhizome of Paris). In our previous studies, saponins from RP exerted antiglioma activity in vitro. However, the effects of PSH on glioma have not been elucidated. The aim of the present study was to evaluate the effects of PSH on U251 glioblastoma cells and elucidate the possible underlying mechanism. The cells were treated with PSH at various concentrations for 48 h, and the cell viability, invasion, apoptosis and cycle progression were assessed using specific assay kits. The activation of Akt, 44/42‑mitogen‑activated protein kinase (MAPK) and the expression levels of A1 adenosine receptor (ARA1) and ARA3 were assessed by western blotting. The results demonstrated that PSH inhibited cell viability, migration and invasion, and induced apoptosis. Treatment of U251 cells with PSH induced the upregulation of p21 and p27, and the downregulation cyclin D1 and S‑phase kinase associated protein 2 protein expression levels, which induced cell cycle arrest at the G1 phase. The results also demonstrated that PSH inhibited the expression of ARA1, and the agonist of ARA1, 2‑chloro‑N6‑cyclopentyladenosine, reversed the effects of PSH. Hypoxia induced increases in the ARA3, hypoxia‑inducible factor‑1α (HIF‑1α) and vascular endothelial growth factor (VEGF) protein expression levels, which were associated with the activation of the Akt and P44/42 MAPK pathways. Compared with the hypoxia group, PSH inhibited the expression levels of ARA3, HIF‑1α and VEGF, as well as the phosphorylation levels of Akt and 44/42 MAPK, and repressed HIF‑1α transcriptional activity. Furthermore, the results demonstrated that PSH inhibited the expression of HIF‑1α by inhibiting the phosphorylation of Akt and 44/42 MAPK mediated by ARA3. Taken together, these results suggested that PSH reduced U251 cell viability via the inhibition of ARA1 and ARA3 expression, and further inhibited Akt and 44/42 MAPK phosphorylation, induced apoptosis and cell cycle arrest.

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