title: Probenecid Sensitizes Neuroblastoma Cancer Stem Cells to Cisplatin.
abstract: We used both in vitro cultures of neuroblastoma cell lines and nude-mice xenotransplants to explore the effects of co-administration of cisplatin and probenecid. Probenecid sensitized neuroblastoma cells, including tumor cells with stem features, to the effects of cisplatin, both in vitro and in vivo. This effect was mediated by an increase in the apoptotic cell death and a concomitant decrease in cell proliferation. This effect is accompanied by modulation of the mRNA and protein of the drug efflux transporters MDR1, MRP2, and BCRP. The co-administration of probenecid with cisplatin should be explored as a possible therapeutic strategy.
authors.affiliation: a Functional Genomics Laboratory , Instituto Nacional de Medicina Genomica , Mexico City 14610 , Mexico.
authors.forename: Denise
authors.initials: D
authors.lastname: Campos-Arroyo
authors.affiliation: a Functional Genomics Laboratory , Instituto Nacional de Medicina Genomica , Mexico City 14610 , Mexico.
authors.forename: Vilma
authors.initials: V
authors.lastname: Maldonado
authors.affiliation: a Functional Genomics Laboratory , Instituto Nacional de Medicina Genomica , Mexico City 14610 , Mexico.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bahena
authors.affiliation: a Functional Genomics Laboratory , Instituto Nacional de Medicina Genomica , Mexico City 14610 , Mexico.
authors.forename: Valeria
authors.initials: V
authors.lastname: Quintanar
authors.affiliation: a Functional Genomics Laboratory , Instituto Nacional de Medicina Genomica , Mexico City 14610 , Mexico.
authors.forename: Nelly
authors.initials: N
authors.lastname: Patiño
authors.affiliation: b Department of Neurophysiology , Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez , Mexico City , Mexico.
authors.forename: Juan
authors.initials: J
authors.lastname: Carlos Martinez-Lazcano
authors.affiliation: a Functional Genomics Laboratory , Instituto Nacional de Medicina Genomica , Mexico City 14610 , Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Melendez-Zajgla
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015870:Gene Expression; D006801:Humans; D008819:Mice, Nude; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000502:physiology; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D011339:Probenecid / Q000008:administration & dosage; D058985:Side-Population Cells / Q000187:drug effects / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D053148:Caspase 3; D002945:Cisplatin; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D011339:Probenecid; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C505407:CASP3 protein, human
keywords: Chemotherapy; Efficacy