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Paeoniflorin exerts antitumor effects by inactivating S phase kinase-associated protein 2 in glioma cells
Jia Ouyang1, Hui Xu1, Ming Li1
1Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Abstract:
Paeoniflorin (PF), a natural compound isolated from Paeoniae radix, has been shown to exert antitumor effects in various types of human cancers including glioma. However, the mechanism of action is not well understood. S-phase kinase-associated protein (Skp)2 functions as an oncogene in many cancers. In the present study, we investigated whether Skp2 mediates the anti-glioma activity of PF. We found that PF inhibited glioma cell proliferation, migration and invasion, and induced G2/M arrest and apoptosis. Skp2 expression was downregulated in glioma cells treated with PF. PF-induced antitumor effects in glioma cells were abolished by Skp2 overexpression but were enhanced by RNA interference of Skp2. Moreover, PF treatment inhibited U87 cell-derived tumor growth in a xenograft mouse model. These results demonstrate that PF exerts its antitumor effects in part by inhibiting Skp2 expression in glioma cells and could be a promising therapeutic agent for glioma therapy.
Insights
Paeoniflorin (PF) inhibits glioma progression by downregulating S-phase kinase-associated protein 2 (Skp2). This natural compound shows promise as a therapeutic agent for glioma, targeting key oncogenic pathways.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Paeoniflorin (PF), derived from Paeoniae radix, exhibits antitumor properties against various cancers, including glioma.
- The precise mechanism underlying PF's anti-glioma effects remains unclear.
- S-phase kinase-associated protein 2 (Skp2) is recognized as an oncogene implicated in numerous cancer types.
Purpose of the Study:
- To investigate if Skp2 mediates the anti-glioma activity of Paeoniflorin (PF).
- To elucidate the molecular mechanisms by which PF exerts its effects on glioma cells.
Main Methods:
- Assessing the impact of PF on glioma cell proliferation, migration, invasion, cell cycle progression (G2/M arrest), and apoptosis.
- Analyzing Skp2 expression levels in PF-treated glioma cells.
- Evaluating the effects of Skp2 overexpression and RNA interference on PF's anti-glioma actions.
- Testing PF's efficacy in a U87 cell-derived xenograft mouse model.
Main Results:
- Paeoniflorin (PF) significantly inhibited glioma cell proliferation, migration, and invasion.
- PF treatment induced G2/M cell cycle arrest and promoted apoptosis in glioma cells.
- PF downregulated Skp2 expression in glioma cells.
- Overexpression of Skp2 abolished PF's anti-glioma effects, while Skp2 inhibition enhanced them.
- PF treatment suppressed tumor growth in a xenograft mouse model.
Conclusions:
- Paeoniflorin (PF) exerts its antitumor effects in glioma, at least partly, by inhibiting Skp2 expression.
- PF demonstrates potential as a therapeutic agent for glioma treatment, targeting Skp2-mediated pathways.
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