Cation Transporter 1 is expressed in lymphoma cells and increases the susceptibility to irinotecan and paclitaxel

Antineoplastic agents directed at nuclear and cytoplasmic targets in tumor cells represent the current mainstay of treatment for patients with disseminated malignant diseases. Cellular uptake of antineoplastics is a prerequisite for their efficacy. Five of six lymphoma cell lines, as well as primary samples from chronic lymphocytic leukemia (CLL) patients, demonstrated significant expression of SLC22A1 mRNA coding for the organic cation transporter 1 (OCT1). Functionally, the antineoplastic agents irinotecan, mitoxantrone and paclitaxel inhibited the uptake of the organic cation [H]MPP into OCT1 transfected CHO model cells, with Ki values of 1.7 μM, 85 μM, and 50 μM, respectively. Correspondingly, OCT1 positive cell lines and transfectants exhibited a significantly higher susceptibility to the cytotoxic effects of irinotecan and paclitaxel as compared to OCT1 negative controls. We hypothesize that OCT1 can contribute to the susceptibility of cancer cells to selected antineoplastic drugs. In the future, expression analysis of transporters and application of transporter-specific antineoplastic agents could help to tailor cancer therapy. This article has not been copyedited and formatted. The final version may differ from this version. JPET Fast Forward. Published on December 27, 2011 as DOI: 10.1124/jpet.111.190561 at A PE T Jornals on Jne 6, 2017 jpet.asjournals.org D ow nladed from