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Inhibition of oncogenic cap-dependent translation by 4EGI-1 reduces growth, enhances chemosensitivity and alters genome-wide translation in non-small cell lung cancer.
De, Arpita; Jacobson, Blake A; Peterson, Mark S; Stelzner, Margaret E; Jay-Dixon, Joe; Kratzke, Marian G; Patel, Manish R; Bitterman, Peter B; Kratzke, Robert A.
Afiliación
  • De A; University of Minnesota, Department of Pharmacology, Minneapolis, MN, USA.
  • Jacobson BA; University of Minnesota, Department of Medicine, Minneapolis, MN, USA.
  • Peterson MS; University of Minnesota, Department of Medicine, Minneapolis, MN, USA.
  • Stelzner ME; University of Minnesota, Department of Medicine, Minneapolis, MN, USA.
  • Jay-Dixon J; University of Minnesota, Department of Medicine, Minneapolis, MN, USA.
  • Kratzke MG; University of Minnesota, Department of Medicine, Minneapolis, MN, USA.
  • Patel MR; University of Minnesota, Department of Medicine, Minneapolis, MN, USA.
  • Bitterman PB; University of Minnesota, Department of Medicine, Minneapolis, MN, USA.
  • Kratzke RA; University of Minnesota, Department of Medicine, Minneapolis, MN, USA. kratz003@umn.edu.
Cancer Gene Ther ; 26(5-6): 157-165, 2019 05.
Article en En | MEDLINE | ID: mdl-30420719
Hyperactivation of eIF4F-mediated translation occurs in many if not all cancers. As a consequence, cancer cells aberrantly enhance expression of malignancy-related proteins that are involved in cell cycle progression, angiogenesis, growth, and proliferation. With this in mind eIF4F is a promising molecular target for therapeutics that counteract pathological eIF4F activity. Here we used 4EGI-1, a small-molecule inhibitor of cap-mediated translation that disrupts formation of the eukaryotic initiation factor 4F (eIF4F) complex to treat non-small cell lung cancer (NSCLC). Treatment of cells with 4EGI-1 reduced cell proliferation, decreased cap-dependent complex formation, induced apoptosis, enhanced sensitivity to gemcitabine, and altered global cellular translation. Suppression of cap-dependent translation by 4EGI-1 resulted in diminished expression of oncogenic proteins c-Myc, Bcl-2, cyclin D1, and survivin, whereas ß-actin expression was left unchanged. In light of these results, small-molecule inhibitors like 4EGI-1 alone or with chemotherapy should be further evaluated in the treatment of NSCLC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiazoles / Carcinoma de Pulmón de Células no Pequeñas / Hidrazonas / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Cancer Gene Ther Asunto de la revista: GENETICA MEDICA / NEOPLASIAS / TERAPEUTICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiazoles / Carcinoma de Pulmón de Células no Pequeñas / Hidrazonas / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Cancer Gene Ther Asunto de la revista: GENETICA MEDICA / NEOPLASIAS / TERAPEUTICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido