Novel multidrug-resistance modulators, KR-30026 and KR-30031, in cancer cells.
Anticancer Res
; 17(6D): 4577-82, 1997.
Article
em En
| MEDLINE
| ID: mdl-9494571
ABSTRACT
The present study was performed to evaluate the ability of KR-30026 and KR-30031 to overcome multidrug resistance (MDR) by measuring the cytotoxicity of paclitaxel and the rate of rhodamine accumulation, which were then compared with verapamil. KR-30026 potentiated the paclitaxel-induced cytotoxicity of HCT15 to over 60 fold greater than that of verapamil, and KR-30031 was equipotent with verapamil (EC50 0.00066, 0.04 and 0.05 nM at 4.0 micrograms/ml, respectively). KR-30026 and KR-30031 were without effect on paclitaxel-induced cytotoxicity to SK-OV-3 cells, as well as on tamoxifen-induced cytotoxicity to HCT15, HCT15/CL02 and SK-OV-3 cells. Maximal rhodamine accumulation by KR-30026, KR-30031 and verapamil were similar in HCT15 cells, while KR-30026 was more potent than verapamil in HCT15/CL02 cells (721 and 440%, respectively). To evaluate the cardiac toxicity of KR-30026 and KR-30031, the changes of tension in isolated rat aorta and left ventricular pressure (LVP) in guinea pig heart were determined; KR-30026 and KR-30031 were 15-40 and 25-70 fold less potent than verapamil, respectively. These results suggest that KR-30026 and KR-30031 are active modulators of MDR with potentially minimal cardiovascular toxicity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasodilatação
/
Sobrevivência Celular
/
Paclitaxel
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Resistência a Múltiplos Medicamentos
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Coração
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Músculo Liso Vascular
Limite:
Animals
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Female
/
Humans
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Male
Idioma:
En
Ano de publicação:
1997
Tipo de documento:
Article