title: 2,3,7,8-Tetrachlorodibenzo-p-dioxin induced cell-specific drug transporters with acquired cisplatin resistance in cisplatin sensitive cancer cells.
abstract: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can induce drug transporter genes such as the ATP-binding cassette G member 2 (ABCG2), which contributes to multidrug resistance. We investigated the effect of TCDD pretreatment on drug transporters induction from cancer cells of various origins. Cell viabilities after treatment of cisplatin were measured to evaluate acquiring cisplatin resistance by TCDD. Acquring cisplatin resistance was found only in cisplatin senstivie cancer cells including gastric SNU601, colon LS180, brain CRT-MG and lymphoma Jurkat cells which showed a significant increase in cell viability after combined treatment with TCDD and cisplatin. High increase of ABCG2 gene expression was found in SNU601 and LS180 cells with a mild increase in the expression of the ABCC3, ABCC5,and SLC29A2 genes in SNU601 cells, and of major vault protein (MVP) in LS180 cells. The AhR inhibitor kaempferol suppressed the upregulation of ABCG2 expression and reversed the TCDD-induced increase in cell viability in LS180 cells. However, in CRT-MG cells, other transporter genes including ABCC1, ABCC5, ABCA3, ABCA2, ABCB4, ABCG1, and SLC29A1 were up-regulated. These findings suggested the acquiring cisplatin resistance by TCDD associated with cancer cell-type-specific induction of drug transporters.
authors.affiliation: Molecular, Cellular and Developmental Biology, Division of Biomedical Science, Graduate School, Korea University, Seoul, Korea. ; Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Tuvshinjargal
authors.identifier: 0000-0001-6174-2022
authors.initials: T
authors.lastname: Gotovdorj
authors.affiliation: Molecular, Cellular and Developmental Biology, Division of Biomedical Science, Graduate School, Korea University, Seoul, Korea. ; Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea. ; Department of Public Health, Graduate School, Korea University, Seoul, Korea. ; Graduate School of Public Health, Korea University, Seoul, Korea.
authors.forename: Eunil
authors.identifier: 0000-0003-1524-5046
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Yongchul
authors.identifier: 0000-0001-9195-0623
authors.initials: Y
authors.lastname: Lim
authors.affiliation: Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Eun Jeong
authors.identifier: 0000-0003-1080-0506
authors.initials: EJ
authors.lastname: Cha
authors.affiliation: Department of Microbiology, College of Medicine, Kwandong University, Gangneung, Korea.
authors.forename: Daeho
authors.identifier: 0000-0003-1314-2587
authors.initials: D
authors.lastname: Kwon
authors.affiliation: Department of Public Health, Graduate School, Korea University, Seoul, Korea.
authors.forename: Eunyoung
authors.identifier: 0000-0002-0329-8004
authors.initials: E
authors.lastname: Hong
authors.affiliation: Graduate School of Public Health, Korea University, Seoul, Korea.
authors.forename: YunJeong
authors.identifier: 0000-0003-0870-4320
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Graduate School of Public Health, Korea University, Seoul, Korea.
authors.forename: Min-Yeong
authors.initials: MY
authors.lastname: Oh
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D033722:Equilibrative-Nucleoside Transporter 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D044949:Kaempferols / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics / Q000378:metabolism; D000099187:Major Vault Protein
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D002945:Cisplatin; D033722:Equilibrative-Nucleoside Transporter 2; D044949:Kaempferols; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C120809:ABCC5 protein, human; C116614:ABCG2 protein, human; C438654:SLC29A2 protein, human; C114462:multidrug resistance-associated protein 3; C006552:kaempferol
keywords: ABCG2; Acquired Cisplatin Resistance; AhR; Drug Transporters; TCDD