title: Dihydromyricetin reverses MRP2-mediated MDR and enhances anticancer activity induced by oxaliplatin in colorectal cancer cells.
abstract: Dihydromyricetin (DMY), extracted from the Chinese herbal medicine Ampelopsis grossedentata, possesses antitumor potential in different types of human cancer cells. Hence, its effects on drug resistance and molecular mechanisms in colorectal cancer (CRC) are still unknown. In our present study, we observed that DMY enhanced the chemosensitivity to oxaliplatin (OXA). DMY increased OXA-induced apoptosis and reduced 5(6)-carboxy-2',7'-dichlorofluorescein accumulation in OXA-resistant CRC HCT116/L-OHP cells. Our mechanistic study suggested that DMY treatment inhibited multidrug resistance protein 2 (MRP2) expression levels and promoter activity, indicating that DMY reduced not only MRP2 transcriptional and translational levels but also its function. Additional experiments indicated that the nuclear translocation of nuclear factor-erythroid 2 p45 related factor 2, a MRP2 regulator, was also inhibited by DMY. In summary, our study provided the first direct evidence that the inhibitory effects of DMY on MRP2 expression in OXA-resistant CRC cells were closely associated with the inhibition of nuclear factor-erythroid 2 p45 related factor 2 signaling. DMY could be a potential candidate for CRC chemotherapy.
authors.affiliation: Departments of aPathology bMedical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Sun
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Feng
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhou
authors.forename: Hua
authors.initials: H
authors.lastname: Sui
authors.forename: Qing
authors.initials: Q
authors.lastname: Ji
authors.forename: Qiukai
authors.initials: Q
authors.lastname: E
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Lili
authors.initials: L
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D044948:Flavonols / Q000008:administration & dosage / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077150:Oxaliplatin; D011401:Promoter Regions, Genetic
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D044948:Flavonols; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D051267:NF-E2-Related Factor 2; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C495635:NFE2L2 protein, human; C472036:dihydromyricetin; C421109:multidrug resistance-associated protein 1