title: Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens.
abstract: Multidrug resistance (MDR) caused by human ABCB1 (P-glycoprotein/MDR1) is one of the major obstacles in chemotherapy. To understand the mechanism of MDR by ABCB1 and circumvent the MDR, in the present study, we established human ABCB1-expressing cells (Flp-In-293/ABCB1 cells) and examined the cytotoxic effects of four guanidine alkaloids from Pterogyne nitens (galegine, nitensidine A, pterogynidine and pterogynine) using Flp-In-293/Mock and Flp-In-293/ABCB1 cells. The activity of ABCB1 in Flp-In-293/ABCB1 cells were confirmed by typical substrates for ABCB1 (taxol and vinblastine) in MTT assay. Flp-In-293/ABCB1 cells were also resistant to the four guanidine alkaloids as well as taxol and vinblastine compared to Flp-In-293/Mock cells although the four guanidine alkaloids exhibited cytotoxicity against the two Flp-In-293 cells. Furthermore, the four guanidine alkaloids were also found to stimulate the ATPase activity of ABCB1 in ATPase assays. These results suggest that ABCB1 can confer the resistance to the cytotoxic guanidine alkaloids by transporting them.
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Bioscience and Biotechnology, Chubu University, Kasugai, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Satake
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Bioscience and Biotechnology, Chubu University, Kasugai, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Tsukamoto
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Bioscience and Biotechnology, Chubu University, Kasugai, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mitani
authors.affiliation: Department of Organic Chemistry, Institute of Chemistry, São Paulo State University, Araraquara, Brazil.
authors.forename: Luis Octavio
authors.initials: LO
authors.lastname: Regasini
authors.affiliation: Department of Organic Chemistry, Institute of Chemistry, São Paulo State University, Araraquara, Brazil.
authors.forename: Vanderlan
authors.initials: V
authors.lastname: da Silva Bolzani
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Bioscience and Biotechnology, Chubu University, Kasugai, Japan.|Department of Applied Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, Kasugai, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagawa
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000470:Alkaloids / Q000008:administration & dosage*; D029911:Caesalpinia / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D003603:Cytotoxins / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000502:physiology*; D006146:Guanidines / Q000008:administration & dosage*; D057809:HEK293 Cells; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000470:Alkaloids; D003603:Cytotoxins; D006146:Guanidines; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513055:ABCB1 protein, human
keywords: ABCB1; ATP-binding cassette (ABC) transporter; P-glycoprotein; guanidine alkaloids