Tangeretin, a citrus pentamethoxyflavone, antagonizes ABCB1-mediated multidrug resistance by inhibiting its transport...

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Multidrug resistance (MDR) and tumor metastasis are primary drivers of chemotherapy failure and cancer mortality.
• ABCB1 transporter overexpression is a significant mechanism contributing to MDR.

Purpose of the Study:

• To investigate the potential of citrus flavonoid tangeretin in overcoming ABCB1-mediated multidrug resistance in cancer.
• To elucidate the mechanism by which tangeretin affects ABCB1 transporter function.

Main Methods:

• Cell-based assays to assess apoptosis, cell cycle arrest, and intracellular drug accumulation.
• Efflux assays in Caco2 cells to evaluate ABCB1 substrate transport.
• ATPase activity assays and molecular docking to determine transporter interaction.

Main Results:

• Tangeretin reversed ABCB1-mediated resistance to chemotherapeutic agents at non-toxic concentrations.
• Co-treatment with tangeretin and paclitaxel induced apoptosis and G2/M cell cycle arrest.
• Tangeretin directly inhibited ABCB1 transporter activity, increasing intracellular drug accumulation and decreasing efflux without altering transporter expression.
• Molecular docking confirmed tangeretin's binding to the ABCB1 transporter.

Conclusions:

• Tangeretin effectively inhibits ABCB1 transporter function, sensitizing resistant cancer cells to chemotherapy.
• Tangeretin demonstrates potential as a therapeutic agent to overcome MDR in cancers.
• Further preclinical and clinical studies are warranted to explore tangeretin's efficacy in resistant cancers.