1. Resistance to cisplatin-induced cell death conferred by the activity of organic anion transporting polypeptides (OATP) in human melanoma cells.
- Author
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Silvy F, Lissitzky JC, Bruneau N, Zucchini N, Landrier JF, Lombardo D, and Verrando P
- Subjects
- Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Hep G2 Cells, Humans, Melanocytes metabolism, Peptides chemistry, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Antineoplastic Agents pharmacology, Apoptosis, Cisplatin pharmacology, Drug Resistance, Neoplasm, Melanoma metabolism, Organic Anion Transporters chemistry
- 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., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2013
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