CPT-11-induced cell death in leukemic cells is not affected by the MDR phenotype.
CPT-11 is a topoisomerase I (Topo I) inhibitor which was initially described as active in multi-drug resistance (MDR) tumors. The MDR phenomenon is characterized by the overexpression of efflux pumps which are able to extrude a range of drugs non-related chemical or functionally. In this work, we treated leukemic cells with CPT-11 300 microM at 24h and compared its cytotoxicity with the activity of efflux pumps and with cell cycle phase. Our findings show that CPT-11 has a potent anti-tumor activity in leukemic cells regardless MDR phenotype and the cell cycle phase, suggesting new avenues to be explored in leukemia treatment.
Silva
Karina L
KL
Laboratório de Hematologia Celular e Molecular, Serviço de Hematologia, Hospital do Câncer (HC-I), Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.
Vasconcelos
Flavia C
FC
Marques-Santos
Luis Fernando
LF
Kwee
Jolie K
JK
Maia
Raquel C
RC
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001773:Blood Cells / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D006801:Humans; D007399:Interphase; D000077146:Irinotecan; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000502:physiology; D010641:Phenotype; D020112:Rhodamine 123; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D000077146:Irinotecan; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020112:Rhodamine 123; D059004:Topoisomerase I Inhibitors