title: Reversal of P-glycoprotein-mediated multidrug resistance is induced by mollugin in MCF-7/adriamycin cells.
abstract: P-glycoprotein (P-gp), an important efflux transporter, is encoded by the MDR1 class of genes and is a central element of the multidrug resistance (MDR) phenomenon in cancer cells. In the present study, we investigated whether mollugin, purified from roots of Rubica cordifolia L., down-regulated MDR1 expression in MCF-7/adriamycin (MCF-7/adr) cells, a human breast multidrug-resistant cancer cell line. Mollugin treatment significantly inhibited MDR1 expression by blocking MDR1 transcription. Mollugin treatment also significantly increased intracellular accumulation of the fluorescently-tagged P-gp substrate, rhodamine-123. The suppression of MDR1 promoter activity and protein expression was mediated through mollugin-induced activation of AMP-activated protein kinase (AMPK). Furthermore, mollugin inhibited MDR1 expression through the suppression of NF-κB and CREB activation. Interestingly, mollugin also inhibited COX-2 expression. These results suggest that mollugin treatment enhanced suppression of P-gp expression by inhibiting the NF-κB signaling pathway and COX-2 expression, as well as attenuating CRE transcriptional activity through AMPK activation.
authors: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea.
authors: Thu Phuong
authors: TP
authors: Tran
authors: Hyung Gyun
authors: HG
authors: Kim
authors: Jae Ho
authors: JH
authors: Choi
authors: Min-Kyun
authors: MK
authors: Na
authors: Hye Gwang
authors: HG
authors: Jeong
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011714:Pyrans / Q000737:chemistry / Q000494:pharmacology*; D020112:Rhodamine 123 / Q000493:pharmacokinetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D005456:Fluorescent Dyes; D016328:NF-kappa B; D011714:Pyrans; D020112:Rhodamine 123; C046245:rubimaillin; D004317:Doxorubicin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases