Unique action determinants of double acting topoisomerase inhibitor, TAS-103.
Int J Oncol
; 19(5): 921-7, 2001 Nov.
Article
em En
| MEDLINE
| ID: mdl-11604989
ABSTRACT
O6-methylguanine-DNA methyltransferase (MGMT), gamma-glutamylcysteine synthetase (gamma-GCS), and glutathione (GSH) are found to participate in resistance to TAS-103, a topoisomerase I/II inhibitor. In 13 human cancer cell lines, MGMT expression correlated with IC50 for TAS-103, whereas gamma-GCS expression inversely correlated with the IC50 value, suggesting MGMT may work to decrease TAS-103 activity but gamma-GCS may increase it. A reduced gamma-GCS and GSH, and an increased MGMT were associated with the development of resistance in A549 and DLD cells, and gamma-GCS inhibition by buthionine sulphoximine increased the TAS-103 resistance, whereas MGMT inhibition by both O6-benzyl-guanine and MGMT-antisense transfection sensitized cells to TAS-103.
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Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Células Tumorais Cultivadas
/
Proteínas de Ligação ao GTP
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Proteínas de Saccharomyces cerevisiae
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Proteínas Mitocondriais
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Inibidores Enzimáticos
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Inibidores da Topoisomerase I
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Inibidores da Topoisomerase II
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Aminoquinolinas
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Indenos
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Japão