Effects of natural nuclear factor-kappa B inhibitors on anticancer drug efflux transporter human P-glycoprotein

Area of Science:

• Oncology
• Pharmacology
• Natural Products Chemistry

Background:

• P-glycoprotein (P-gp) is a key drug efflux transporter in multidrug resistance (MDR).
• Nuclear factor-kappa B (NF-κB) signaling pathways are crucial in cancer development and progression.
• Inhibiting P-gp and NF-κB may overcome MDR and improve cancer treatment outcomes.

Purpose of the Study:

• To investigate the effects of natural compounds that inhibit NF-κB activation on P-glycoprotein function.
• To determine if these natural compounds can reverse MDR in cancer cells.
• To explore the potential of these compounds in enhancing cancer chemotherapy.

Main Methods:

• Utilized human MDR1 gene-transfected KB/MDR1 cells to study P-glycoprotein function.
• Assessed the accumulation of P-gp substrates (daunorubicin, rhodamine 123) in cells treated with natural compounds.
• Measured P-glycoprotein ATPase activity and NF-κB activation stimulated by TNF-α.
• Evaluated the sensitization of cells to vinblastine cytotoxicity.

Main Results:

• Caffeic acid phenethyl ester (CAPE), licochalcone A, anacardic acid, celastrol, xanthohumol, magnolol, and honokiol increased P-gp substrate accumulation and stimulated P-gp ATPase activity.
• CAPE, licochalcone A, anacardic acid, and xanthohumol inhibited TNF-α-induced NF-κB activation.
• These compounds sensitized KB/MDR1 cells to vinblastine, indicating MDR reversal.
• Lupeol, zerumbone, thymoquinone, emodin, and anethol showed no significant effects on P-gp function.

Conclusions:

• Natural compounds like CAPE, licochalcone A, and anacardic acid exhibit dual inhibition of P-glycoprotein and NF-κB.
• These compounds effectively reverse multidrug resistance in cancer cells.
• They hold promise as adjuncts to enhance the efficacy of conventional cancer chemotherapy.