title: Effects of natural nuclear factor-kappa B inhibitors on anticancer drug efflux transporter human P-glycoprotein.
abstract: Drug efflux transporter P-glycoprotein plays an important role in cancer chemotherapy. The nuclear factor-κB (NF-κB) transcription factors play critical roles in development and progression of cancer. In this study, the effects of natural compounds that can inhibit NF-κB activation on the function of P-glycoprotein were investigated using human MDR1 gene-transfected KB/MDR1 cells. The accumulation of daunorubicin or rhodamine 123, fluorescent substrates of P-glycoprotein, in KB/MDR1 cells increased in the presence of caffeic acid phenetyl ester (CAPE), licochalcone A, anacardic acid, celastrol, xanthohumol, magnolol, and honokiol in a concentration-dependent manner. In contrast, lupeol, zerumbone, thymoquinone, emodin, and anethol had no effects. The ATPase activities of P-glycoprotein were stimulated by CAPE, licochalcone A, anacardic acid, celastrol, xanthohumol, magnolol, and honokiol. Tumor necrosis factor (TNF)-α stimulated NF-κB activation was inhibited by CAPE, licochalcone A, anacardic acid, and xanthohumol. KB/MDR1 cells were sensitized to vinblastine cytotoxicity by CAPE, licochalcone A, anacardic acid, xanthohumol, magnolol, and honokiol, showing that these natural NF-κB inhibitors reverse multidrug resistance. These results suggest that natural compounds, such as CAPE, licochalcone A, and anacardic acid, have dual inhibitory effects on the anticancer drug efflux transporter P-glycoprotein and NF-κB activation, and may become useful to enhance the efficacy of cancer chemotherapy.
authors.affiliation: School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya, Aichi 464-8650, Japan; Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan. Electronic address: nabekura@dpc.agu.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nabekura
authors.affiliation: Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hiroi
authors.affiliation: School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya, Aichi 464-8650, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya, Aichi 464-8650, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Uwai
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D017705:Lignans / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011427:Propiophenones / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001688:Biological Products; D001713:Biphenyl Compounds; D005419:Flavonoids; D017705:Lignans; D016328:NF-kappa B; D011427:Propiophenones; C005498:magnolol; C104536:xanthohumol
keywords: Anticancer drug; Drug transporter; NF-κB; P-glycoprotein; Phytochemical