TY - JOUR
T1 - Characterization of the organic cation transporter SLC22A16
T2 - A doxorubicin importer
AU - Okabe, Mitsunori
AU - Unno, Michiaki
AU - Harigae, Hideo
AU - Kaku, Mitsuo
AU - Okitsu, Yoko
AU - Sasaki, Takeshi
AU - Mizoi, Takayuki
AU - Shiiba, Kenichi
AU - Takanaga, Hitomi
AU - Terasaki, Tetsuya
AU - Matsuno, Seiki
AU - Sasaki, Iwao
AU - Ito, Sadayoshi
AU - Abe, Takaaki
PY - 2005/8/5
Y1 - 2005/8/5
N2 - 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 μM. In cytotoxic assays, stable transfectants of leukemic Jurkat cells overexpressing SLC22A16 cells became significantly more sensitive to doxorubicin (2 μM) treatment. Characterization of SLC22A16 will help in designing novel therapies targeting hematological malignancies.
AB - 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 μM. In cytotoxic assays, stable transfectants of leukemic Jurkat cells overexpressing SLC22A16 cells became significantly more sensitive to doxorubicin (2 μM) treatment. Characterization of SLC22A16 will help in designing novel therapies targeting hematological malignancies.
KW - Doxorubicin
KW - Drug resistance
KW - Influx transporter
KW - Leukemia
KW - Molecular targets for therapy
KW - Organic cation transporter
KW - SLC22A16
UR - http://www.scopus.com/inward/record.url?scp=20744450287&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20744450287&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2005.05.174
DO - 10.1016/j.bbrc.2005.05.174
M3 - Article
C2 - 15963465
AN - SCOPUS:20744450287
SN - 0006-291X
VL - 333
SP - 754
EP - 762
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
