Differential effects of calcium antagonists on ABCG2/BCRP-mediated drug             resistance and transport in SN-38-resistant HeLa cells.
The effects of 9 calcium antagonists on ABCG2/BCRP-mediated resistance and             transport were examined in HeLa and SN-38-resistant HeLa (HeLa/SN100) cells, overexpressing             ABCG2/BCRP. Sensitivity to mitoxantrone, an ABCG2/BCRP substrate, in HeLa/SN100             cells was significantly reversed by the coexistence of the calcium antagonists,             except for diltiazem and verapamil. The accelerated transport activity of Hoechst33342,             an ABCG2/BCRP substrate, in HeLa/SN100 cells was significantly decreased by the             presence of the calcium antagonists, except for diltiazem, nifedipine or verapamil,             returning to the level of HeLa cells. The present study classifies the calcium             antagonists into 3 categories: strong (benidipine, felodipine, nicardipine, nisoldipine             and nitrendipine), moderate (amlodipine and nifedipine) and weak (diltiazem and             verapamil) inhibitors of ABCG2/BCRP.
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji 670-8524, Japan. takara@gm.himeji-du.ac.jp
Kohji
K
Takara
Mika
M
Matsubara
Kazuhiro
K
Yamamoto
Tetsuya
T
Minegaki
Shigehiko
S
Takegami
Minoru
M
Takahashi
Teruyoshi
T
Yokoyama
Katsuhiko
K
Okumura
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D009363:Neoplasm Proteins; C017807:bisbenzimide ethoxide trihydrochloride