Abstract

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 patients demonstrated significant expression of SLC22A1 mRNA coding for organic cation transporter 1 (OCT1). Functionally, the antineoplastic agents irinotecan, mitoxantrone, and paclitaxel inhibited the uptake of the organic cation [³H]1-methyl-4-pyridinium iodide into OCT1-transfected Chinese hamster ovary model cells, with K_i values of 1.7, 85, and 50 μM, respectively. Correspondingly, OCT1-positive cell lines and transfectants exhibited significantly higher susceptibilities to the cytotoxic effects of irinotecan and paclitaxel compared with those of OCT1-negative controls. We hypothesize that OCT1 can contribute to the susceptibility of cancer cells to selected antineoplastic drugs. In the future, an expression analysis of the transporters and the application of transporter-specific antineoplastic agents could help to tailor cancer therapy.