Modulation of P-glycoprotein Expression by Honokiol, Magnolol and 4-O-methylhonokiol, the Bioactive Components of Magnolia Officinalis

Aim: This study aimed to evaluate the effect of honokiol and its structural analogs on the functional activity and gene expression of P-glycoprotein (P-gp) in order to identify effective P-gp inhibitors from natural products which have additional health-promoting effects.

Materials And Methods: The interaction characteristics of honokiol, magnolol and 4-O-methylhonokiol with P-gp were determined in NCI/ADR-RES cells overexpressing P-gp.

Results: All three compounds down-regulated the expression of P-gp in a concentration- and time-dependent manner, leading to 2.5- to 4.1-fold reductions of P-gp expression in NCI/ADR-RES cells. Accordingly, down-regulation of P-gp resulted in the significant enhancement of the intracellular accumulation of calcein, a P-gp substrate. Furthermore, pre-treatment with honokiol, magnolol or 4-O-methylhonokiol significantly increased the susceptibility of cancer cells to daunorubicin-induced cytotoxicity in NCI/ADR-RES cells.

Conclusion: The present study suggests that honokiol, magnolol and 4-O-methylhonokiol could be promising agents for reducing the multidrug resistance of cancer cells to anticancer drugs via the down-regulation of P-gp expression.