NP-1250, an ABCG2 inhibitor, induces apoptotic cell death in mitoxantrone-resistant             breast carcinoma MCF7 cells via a caspase-independent pathway.
Chemoresistance is one of the main obstacles to successful cancer therapy             and is frequently associated with multidrug resistance (MDR). One of the most             studied mechanisms of MDR is the high expression of ATP-binding cassette (ABC)             transporters. Here, we demonstrated that NP-1250, an ABCG2 inhibitor, induced             apoptotic cell death in ABCG2-overexpressing multidrug-resistant MCF7/mitoxantrone-resistant             (MX) human breast carcinoma cells via a caspase-independent pathway. Incubation             of MCF7/MX cells with NP-1250 significantly reduced cell viability, while NP-1250             had little effect on the viability of drug-sensitive MCF7/wild-type cells. Although             the target molecules of NP-1250 in cell death remain unknown, investigation of             NP-1250 will aid in the elucidation of the molecular mechanism of drug resistance             and NP-1250 may become a new therapy for MDR cancers.
Department of Pathology and Oncology, Juntendo University School of Medicine, Bunkyo, Tokyo 113-8421, Japan.
Masumi
M
Ito
Kazunori
K
Kajino
Masaaki
M
Abe
Tsutomu
T
Fujimura
Reiko
R
Mineki
Takako
T
Ikegami
Toshihisa
T
Ishikawa
Okio
O
Hino
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008942:Mitoxantrone / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D008942:Mitoxantrone; D020169:Caspases