RT Journal Article
SR Electronic
T1 Human Organic Cation Transporter 1 Is Expressed in Lymphoma Cells and Increases Susceptibility to Irinotecan and Paclitaxel
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 16
OP 23
DO 10.1124/jpet.111.190561
VO 341
IS 1
A1 Shivangi Gupta
A1 Gerald Wulf
A1 Maja Henjakovic
A1 Hermann Koepsell
A1 Gerhard Burckhardt
A1 Yohannes Hagos
YR 2012
UL http://jpet.aspetjournals.org/content/341/1/16.abstract
AB 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 Ki 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.