title: Interactions of ofloxacin and erythromycin with the multidrug resistance protein (MRP) in MRP-overexpressing human leukemia cells.
abstract: To investigate interactions between the multidrug resistance protein (MRP) and antimicrobial agents, we examined the effects of 12 agents on vincristine sensitivity and efflux of the calcein acetoxy-methyl ester (calcein-AM) of a MRP substrate in MRP-overexpressing cells. Only ofloxacin and erythromycin enhanced sensitivity with increased intracellular vincristine accumulation and inhibited the calcein-AM efflux. Our findings suggest that the two agents are possible MRP substrates and may competitively inhibit MRP function as a drug efflux pump.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Terashi
authors.forename: M
authors.initials: M
authors.lastname: Oka
authors.forename: H
authors.initials: H
authors.lastname: Soda
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: S
authors.initials: S
authors.lastname: Kawabata
authors.forename: K
authors.initials: K
authors.lastname: Nakatomi
authors.forename: K
authors.initials: K
authors.lastname: Shiozawa
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Noguchi
authors.forename: M
authors.initials: M
authors.lastname: Suenaga
authors.forename: C
authors.initials: C
authors.lastname: Tei
authors.forename: S
authors.initials: S
authors.lastname: Kohno
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D004917:Erythromycin / Q000494:pharmacology* / Q000627:therapeutic use; D005452:Fluoresceins / Q000378:metabolism; D019450:Genes, MDR; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015242:Ofloxacin / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D005452:Fluoresceins; D014750:Vincristine; D004917:Erythromycin; D015242:Ofloxacin; C007740:fluorexon