title: Resistance to cisplatin-induced cell death conferred by the activity of organic anion transporting polypeptides (OATP) in human melanoma cells.
abstract: Expression of organic anion transporting polypeptides (OATP) transporters can be modified with potential incidence in cancers, yet they have not been considered in melanoma. Here, we demonstrate transcriptional and protein expression of OATP members in human melanoma cell lines with sodium-independent organic anion uptake activity. Importantly, uptake of different organic anions over 24 h led to a common resistance signal to apoptotic cell death, induced further by cisplatin in 24 h. The mechanism is not dependent on the transport of cisplatin by the OATP, as it is not an OATP substrate. The resistance signal was modulated by PKC, disclosing it as signal mediator. This study suggests that OATP, which can be constantly activated by endobiotics, may contribute to melanoma chemotherapeutic resistance, thereby justifying the development of OATP targeting strategies.
authors.affiliation: Aix-Marseille University, INSERM UMR911 (CRO2), Marseille, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Silvy
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lissitzky
authors.forename: Nadine
authors.initials: N
authors.lastname: Bruneau
authors.forename: Nathalie
authors.initials: N
authors.lastname: Zucchini
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Landrier
authors.forename: Dominique
authors.initials: D
authors.lastname: Lombardo
authors.forename: Patrick
authors.initials: P
authors.lastname: Verrando
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D027361:Organic Anion Transporters; D010455:Peptides; D002945:Cisplatin