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Oxaliplatin-induced neurotoxicity is dependent on the organic cation transporter OCT2.
Sprowl, Jason A; Ciarimboli, Giuliano; Lancaster, Cynthia S; Giovinazzo, Hugh; Gibson, Alice A; Du, Guoqing; Janke, Laura J; Cavaletti, Guido; Shields, Anthony F; Sparreboom, Alex.
Afiliación
  • Sprowl JA; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Proc Natl Acad Sci U S A ; 110(27): 11199-204, 2013 Jul 02.
Article en En | MEDLINE | ID: mdl-23776246
Oxaliplatin is an integral component of colorectal cancer therapy, but its clinical use is associated with a dose-limiting peripheral neurotoxicity. We found that the organic cation transporter 2 (OCT2) is expressed on dorsal root ganglia cells within the nervous system where oxaliplatin is known to accumulate. Cellular uptake of oxaliplatin was increased by 16- to 35-fold in cells overexpressing mouse Oct2 or human OCT2, and this process was associated with increased DNA platination and oxaliplatin-induced cytotoxicity. Furthermore, genetic or pharmacologic knockout of Oct2 protected mice from hypersensitivity to cold or mechanical-induced allodynia, which are established tests to assess acute oxaliplatin-induced neurotoxicity. These findings provide a rationale for the development of targeted approaches to mitigate this debilitating toxicity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organoplatinos / Síndromes de Neurotoxicidad / Proteínas de Transporte de Catión Orgánico Límite: Animals / Female / Humans / Male Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organoplatinos / Síndromes de Neurotoxicidad / Proteínas de Transporte de Catión Orgánico Límite: Animals / Female / Humans / Male Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos