Characterization of the organic cation transporter SLC22A16: a doxorubicin importer.

Abstract

Specific efflux transporters, such as P-glycoprotein, have been shown to confer drug resistance by decreasing the intracellular accumulation of anticancer drugs. Understanding influx transporters, as well as efflux transporters, is essential to overcome this resistance. We report the expression profile and pharmacological characterization of an organic cation transporter, SLC22A16. The results of our experiments indicate that SLC22A16 is a mediator of doxorubicin uptake in cancer cells. Quantitative real-time RT-PCR analyses show that SLC22A16 is expressed in primary samples taken from patients with acute leukemia. Xenopus oocytes injected with SLC22A16 cRNA import doxorubicin, a widely used anticancer drug for hematological malignancies, in a saturable and dose-dependent manner. The apparent Km value for doxorubicin import was 5.2+/-0.4 microM. In cytotoxic assays, stable transfectants of leukemic Jurkat cells overexpressing SLC22A16 cells became significantly more sensitive to doxorubicin (2 microM) treatment. Characterization of SLC22A16 will help in designing novel therapies targeting hematological malignancies.

• Authors: Mitsunori Okabe, Michiaki Unno, Hideo Harigae, Mitsuo Kaku, Yoko Okitsu, Takeshi Sasaki, Takayuki Mizoi, Kenichi Shiiba, Hitomi Takanaga, Tetsuya Terasaki, Seiki Matsuno, Iwao Sasaki, Sadayoshi Ito, Takaaki Abe
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 333 Issue 3 Pg. 754-62 (Aug 05 2005) ISSN: 0006-291X [Print] United States
• PMID: 15963465 (Publication Type: Journal Article)

Chemical References

• Antibiotics, Antineoplastic
• DNA Primers
• RNA, Messenger
• Doxorubicin

Topics

• Antibiotics, Antineoplastic (metabolism, pharmacology)
• Base Sequence
• Cell Line, Tumor
• DNA Primers
• Doxorubicin (metabolism, pharmacology)
• Humans
• Jurkat Cells
• RNA, Messenger (genetics)
• Reverse Transcriptase Polymerase Chain Reaction