title: Oroxylin A reverses P-glycoprotein-mediated multidrug resistance of MCF7/ADR cells by G2/M arrest.
abstract: Oroxylin A is a naturally occurring monoflavonoid isolated from the root of Scutellaria baicalensis Georgi, which has been used in traditional Chinese medicine for its anti-tumor, anti-inflammatory and anti-bacterial properties. The purpose of this study is to investigate the reversal effect and the fundamental mechanisms of oroxylin A in MCF7/ADR cells. Data indicated that oroxylin A showed strong reversal potency in MCF7/ADR cells and the reversal fold (RF) reached 4.68. After treatment with oroxylin A, MCF7/ADR cells displayed reduced functional activity and expression of MDR1 at both the protein and mRNA levels. Meanwhile, oroxylin A induced cells G2/M arrest in a concentration-dependent manner by increasing the expression of p-Chk2 (Thr68). Moreover, western blot and EMSA assays were used to reveal the inhibition of NF-κB in nucleus and the suppression of NF-κB binding activity by oroxylin A. NSC 109555 ditosylate-Chk2 inhibitor partly dismissed G2/M arrest induced by oroxylin A, reversed the increased trend of p-Chk2 and p-P53 (Ser20), inhibited the decreasing effect of oroxylin A on the expression of P-gp and decreased the reversal fold of 90 μM oroxylin A from 4.68 fold to 1.73 fold. In conclusion, we suggested that oroxylin A reversed MDR by G2/M arrest and the underlying mechanism attributed to the suppression of P-gp expression via Chk2/P53/NF-κB signaling pathway.
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, People's Republic of China.
authors.forename: Litao
authors.initials: L
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Hu
authors.initials: H
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Di
authors.initials: D
authors.lastname: Pan
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Li
authors.forename: Guanzhong
authors.initials: G
authors.lastname: Wu
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D064447:Checkpoint Kinase 2; D004396:Coloring Agents; D018432:Drug Resistance, Multiple / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016195:G2 Phase / Q000187:drug effects*; D016158:Genes, p53 / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics; D011419:Propidium; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020112:Rhodamine 123; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids; D005456:Fluorescent Dyes; D016328:NF-kappa B; D013778:Tetrazolium Salts; D013844:Thiazoles; D020112:Rhodamine 123; D011419:Propidium; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; C022616:thiazolyl blue