title: Dioscin restores the activity of the anticancer agent adriamycin in multidrug-resistant human leukemia K562/adriamycin cells by down-regulating MDR1 via a mechanism involving NF-κB signaling inhibition.
abstract: The purpose of this study was to investigate the ameliorating effect of dioscin (1) on multidrug resistance (MDR) in adriamycin (ADR)-resistant erythroleukemic cells (K562/adriamycin, K562/ADR) and to clarify the molecular mechanisms involved. High levels of multidrug resistance 1 (MDR1) mRNA and protein and reduced ADR retention were found in K562/ADR cells compared with parental cells (K562). Dioscin (1), a constituent of plants in the genus Discorea, significantly inhibited MDR1 mRNA and protein expression and MDR1 promoter and nuclear factor κ-B (NF-κB) activity in K562/ADR cells. MDR1 mRNA and protein suppression resulted in the subsequent recovery of intracellular drug accumulation. Additionally, inhibitor κB-α (IκB-α) degradation was inhibited by 1. Dioscin (1) reversed ADR-induced MDR by down-regulating MDR1 expression by a mechanism that involves the inhibition of the NF-κB signaling pathway. These findings provide evidence to support the further investigation of the clinical application of dioscin (1) as a chemotherapy adjuvant.
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Meng
authors.forename: Changyuan
authors.initials: C
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Huo
authors.forename: Huijun
authors.initials: H
authors.lastname: Sun
authors.forename: Xiaochi
authors.initials: X
authors.lastname: Ma
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D027742:Dioscorea / Q000737:chemistry; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000187:drug effects; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy; D008156:Luciferases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; C019357:dioscin; D004317:Doxorubicin; D008156:Luciferases; D004144:Diosgenin