Quercetin Inhibits KBM7R Cell Proliferation through Wnt/β-Catenin Signaling

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Tyrosine kinase inhibitors (TKIs) are effective for chronic myelogenous leukemia (CML) but fail in patients with the T315I mutation.
• Quercetin (Qu), a bioflavonoid with antitumor properties, is investigated for overcoming TKI resistance.

Purpose of the Study:

• To evaluate the effect of Quercetin (Qu) on cell proliferation and the Wnt/β-catenin pathway in KBM7R cells.
• To explore Quercetin as a potential therapeutic agent against imatinib-resistant CML with the T315I mutation.

Main Methods:

• KBM7R cells (imatinib-resistant, T315I mutation) were treated with varying concentrations of Quercetin (Qu).
• Cell proliferation was assessed using trypan blue staining to determine IC50.
• Apoptosis and cell cycle were analyzed by flow cytometry (FCM).
• mRNA and protein expression of key signaling molecules were evaluated via RT-PCR and Western blot.

Main Results:

• Quercetin inhibited KBM7R cell proliferation with an IC50 of 241.7 μmol/L after 48 hours.
• Quercetin treatment (50-200 μmol/L) increased apoptosis and induced G1 phase cell cycle arrest.
• Quercetin upregulated apoptosis-related proteins (caspase-3, -8, -9) and cell cycle inhibitors (p21, p27).
• Quercetin downregulated Wnt/β-catenin pathway components (GSK-3β, β-catenin, Lef-1) and downstream targets (PPAR-δ, cyclin D1) in both KBM7 and KBM7R cells.

Conclusions:

• Quercetin effectively inhibits proliferation, induces apoptosis, and arrests the cell cycle in imatinib-resistant KBM7R cells harboring the T315I mutation.
• The observed anti-cancer effects of Quercetin are associated with the suppression of the Wnt/β-catenin signaling pathway.
• Quercetin demonstrates potential as a therapeutic agent for TKI-resistant CML.