Enhanced cytotoxicity and nuclear accumulation of doxorubicin-loaded nanospheres in human breast cancer MCF7 cells expressing MRP1.
Previous studies have demonstrated that doxorubicin (DOX) encapsulated in polyisohexylcyano-acrylate nanospheres (NS-DOX) circumvented the resistance of breast cancer cells overexpressing P-glycoprotein (Pgp). Another protein is involved in multidrug resistance phenotype, the multidrug resistance associated protein (MRP1). We report that NS-DOX overcomes multidrug resistance in breast cancer cells overexpressing MRP1. Taking into account that anthracyclines are conjugated to or co-transported with glutathione by MRP1, these data suggest that probably due to ion pair formation (NS-DOX), MRP1 could not transport the anthracycline. Pgp is probably able to transport the ion pair drug complex and the mechanisms of drug resistance reversion in Pgp expressing cells need to be further elucidated.
Aouali
Nasséra
N
Unité MéDIAN CNRS UMR6142, IFR53, UFR de Pharmacie, 51096 Reims cedex, France.
Morjani
Hamid
H
Trussardi
Aurélie
A
Soma
Emilienne
E
Giroux
Bruno
B
Manfait
Michel
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism*; D004396:Coloring Agents / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000903:Antibiotics, Antineoplastic; D004396:Coloring Agents; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; C116614:ABCG2 protein, human; C022616:thiazolyl blue; C421109:multidrug resistance-associated protein 1