Cisplatin and Oxaliplatin, but Not Carboplatin and Nedaplatin, Are Substrates for Human Organic Cation Transporters (SLC22A1–3 and Multidrug and Toxin Extrusion Family)

  title={Cisplatin and Oxaliplatin, but Not Carboplatin and Nedaplatin, Are Substrates for Human Organic Cation Transporters (SLC22A1–3 and Multidrug and Toxin Extrusion Family)},
  author={Atsushi Yonezawa and Satohiro Masuda and Sachiko Yokoo and Toshiya Katsura and Ken-ichi Inui},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  pages={879 - 886}
  • A. Yonezawa, S. Masuda, K. Inui
  • Published 1 November 2006
  • Biology, Chemistry
  • Journal of Pharmacology and Experimental Therapeutics
We have examined the role of the human organic cation transporters [hOCTs and human novel organic cation transporter (hOCTN); SLC22A1–5] and apical multidrug and toxin extrusion (hMATE) in the cellular accumulation and cytotoxicity of platinum agents using the human embryonic kidney (HEK) 293 cells transiently transfected with the transporter cDNAs. Both the cytotoxicity and accumulation of cisplatin were enhanced by the expression of hOCT2 and weakly by hOCT1, and those of oxaliplatin were… 

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[Platinum agent-induced nephrotoxicity via organic cation transport system].
  • A. Yonezawa
  • Biology, Chemistry
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
  • 2012
Oxaliplatin, which was a superior substrate of the luminal efflux transporter, MATE2-K as well as OCT2, did not show nephrotoxicity and carboplatin and nedaplatin were not transported by these transporters.
The human organic cation transporter OCT1 mediates high affinity uptake of the anticancer drug daunorubicin
Using the high-grade serous ovarian cancer cell line TOV2223G, it is shown that OCT1 mediated the high affinity uptake of daunorubicin into the cells, and that micromolar amounts of choline completely abolished the drug entry.


Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2.
Cloning and characterization of two human polyspecific organic cation transporters.
Cl cloning and characterization of two homologous transporters from man (hOCT1 and hOCT2) displaying approximately 80% amino acid identity to rOCT 1 and rO CT2 are reported, respectively.
Pharmacological and Physiological Functions of the Polyspecific Organic Cation Transporters: OCT1, 2, and 3 (SLC22A1-3)
The recent identification of polymorphic genetic variants of human OCT1 and OCT2 that severely affect transport activity suggests that some of the interpatient differences in response and sensitivity to cationic drugs may be caused by variable activity of these transporters.
Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2.
Results indicate that hMATE2-K is a new human kidney-specific H+/organic cation antiporter that is responsible for the tubular secretion of cationic drugs across the brush border membranes.
A human transporter protein that mediates the final excretion step for toxic organic cations.
It is shown that MATE1, a human and mouse orthologue of the multidrug and toxin extrusion family conferring multidrog resistance on bacteria, is primarily expressed in the kidney and liver, where it is localized to the luminal membranes of the urinary tubules and bile canaliculi.
Creatinine Transport by Basolateral Organic Cation Transporter hOCT2 in the Human Kidney
It is suggested that hOCT2, but not hO CT1, is responsible for the basolateral membrane transport of creatinine in the human kidney.
Cloning and Functional Characterization of a Potential-sensitive, Polyspecific Organic Cation Transporter (OCT3) Most Abundantly Expressed in Placenta*
A cDNA isolated from rat placenta which, when expressed heterologously, mediates the transport of a wide spectrum of organic cations, represents a new member of the OCT gene family.