Characterization of the organic cation transporter SLC22A16: a doxorubicin importer.
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.
Okabe
Mitsunori
M
Division of General and Alimentary Tract Surgery, Department of Surgery, Tohoku University School of Medicine, Japan. okabem@mail.nih.gov
Unno
Michiaki
M
Harigae
Hideo
H
Kaku
Mitsuo
M
Okitsu
Yoko
Y
Sasaki
Takeshi
T
Mizoi
Takayuki
T
Shiiba
Kenichi
K
Takanaga
Hitomi
H
Terasaki
Tetsuya
T
Matsuno
Seiki
S
Sasaki
Iwao
I
Ito
Sadayoshi
S
Abe
Takaaki
T
D000903:Antibiotics, Antineoplastic / Q000378:metabolism* / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000903:Antibiotics, Antineoplastic; D017931:DNA Primers; D012333:RNA, Messenger; D004317:Doxorubicin