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  • Title: Modulation of P-glycoprotein expression by honokiol, magnolol and 4-O-methylhonokiol, the bioactive components of Magnolia officinalis.
    Author: Han HK, Van Anh LT.
    Journal: Anticancer Res; 2012 Oct; 32(10):4445-52. PubMed ID: 23060571.
    Abstract:
    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.
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