Synergistic Activity of an Antimetabolite Drug and Tyrosine Kinase Inhibitors against Breast Cancer Cells.
Chem Pharm Bull (Tokyo)
; 65(8): 768-775, 2017 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-28539531
ABSTRACT
Antimetabolite drugs, including the adenosine deaminase inhibitor cladribine, have been shown to induce apoptosis in a variety of cancer cells, and have been widely used in clinical trials of various cancers in conjunction with tyrosine kinase inhibitors (TKIs). Combination treatment with cladribine and gefitinib or dasatinib is expected to have a synergistic inhibitory effect on breast cancer cell growth. Our results demonstrated that the combination treatment had synergistic activity against human breast cancer (MCF-7) cells, enhanced G2/M cell arrest and reactive oxygen species (ROS) generation, and increased the loss of mitochondrial membrane potential and cell apoptosis. In addition, the combination treatment decreased Bcl-2 expression. Our results demonstrated that cladribine in combination with gefitinib or dasatinib exerted synergistic anticancer effects on MCF-7 cells by inducing cell cycle arrest, ROS production and apoptosis through the mitochondria-mediated intrinsic pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Tirosina Quinasas
/
Neoplasias de la Mama
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Cladribina
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Inhibidores de Proteínas Quinasas
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Antineoplásicos
Límite:
Female
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Humans
Idioma:
En
Revista:
Chem Pharm Bull (Tokyo)
Año:
2017
Tipo del documento:
Article