Modulation of P-glycoprotein expression by honokiol, magnolol and 4-O-methylhonokiol, the bioactive components of Magnolia officinalis.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
College of Pharmacy, Dongguk University-Seoul, Pil-dong-3ga, Jung-gu, Seoul 100-715, Korea.  hkhan@dongguk.edu.
Hyo-Kyung
HK
Han
Luu Thi
LT
Van Anh
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D000498:Allyl Compounds; D010636:Phenols
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D003630:Daunorubicin; D017705:Lignans; D010936:Plant Extracts; C542058:4-O-methylhonokiol; C005498:magnolol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols