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Quercetin induces apoptosis in meningioma cells through the miR-197/IGFBP5 cascade
Shun-An Hu1, Jin Cheng2, Wo-Hua Zhao1
1Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 4430022, China.
Abstract:
To investigate the effects of quercetin on cell viability and apoptosis in meningioma cells and to determine the underlying molecular mechanism. HBL-52 meningioma cells were treated with quercetin at doses of 1, 5, 10, 20, and 40 ng/mL for 24, 36 and 48 h, and cell viability was assessed using the Cell Counting kit-8 (CCK-8) test. Apoptosis was determined by flow cytometry. Bax, Bcl-2, and IGFBP5 protein expression was assessed by western blot, and IGFBP5 and miR-197 mRNA levels were measured using quantitative reverse transcription PCR (qRT-PCR). The interaction between miR-197 and IGFBP5 was verified by dual luciferase assay. Quercetin reduces viability and proliferation and increases apoptosis in HBL-52 cells in a dose- and time-dependent manner. Quercetin treatment also decreases Bcl-2 and increases Bax protein expression, and increases miR-197 mRNA while reducing IGFBP5 mRNA expression. A dual luciferase assay showed that miR-197 interacts directly with binding sites in the 3'untranslated region of IGFBP5, and that miR-197 overexpression reduced IGFBP5 expression. Quercetin may reduce meningioma cell proliferation and increase apoptosis by activating the miR-197/IGFBP5 cascade and regulating Bcl-2/Bax.
Insights
Quercetin, a natural compound, effectively reduces meningioma cell growth and promotes apoptosis. It achieves this by modulating the miR-197/IGFBP5 pathway and regulating key proteins involved in cell death.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Meningioma is a primary brain tumor with limited effective treatments.
- Understanding the molecular mechanisms underlying meningioma growth is crucial for developing novel therapies.
- Natural compounds like quercetin show potential in cancer treatment.
Purpose of the Study:
- To investigate the anti-cancer effects of quercetin on meningioma cells.
- To elucidate the molecular mechanisms, including apoptosis and gene expression changes, involved in quercetin's action.
- To explore the role of the miR-197/IGFBP5 pathway in quercetin-treated meningioma cells.
Main Methods:
- HBL-52 meningioma cells were treated with varying doses and time points of quercetin.
- Cell viability was assessed using the Cell Counting kit-8 (CCK-8) assay.
- Apoptosis, protein expression (Bax, Bcl-2, IGFBP5), and mRNA levels (IGFBP5, miR-197) were analyzed using flow cytometry, western blot, and qRT-PCR, respectively.
- The interaction between miR-197 and IGFBP5 was confirmed via a dual luciferase assay.
Main Results:
- Quercetin demonstrated a dose- and time-dependent reduction in HBL-52 cell viability and proliferation.
- Apoptosis was significantly increased in quercetin-treated cells.
- Quercetin altered the expression of apoptosis-related proteins (decreased Bcl-2, increased Bax) and modulated gene expression (increased miR-197 mRNA, decreased IGFBP5 mRNA).
- The dual luciferase assay confirmed a direct interaction between miR-197 and IGFBP5, with miR-197 overexpression leading to reduced IGFBP5 expression.
Conclusions:
- Quercetin exhibits significant anti-proliferative and pro-apoptotic effects on meningioma cells.
- The miR-197/IGFBP5 signaling pathway is a key mediator of quercetin's anti-cancer activity in meningioma.
- Quercetin's therapeutic potential in meningioma may involve the regulation of the miR-197/IGFBP5 cascade and the Bcl-2/Bax balance.
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