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Artículo

Enhanced cytotoxicity of an anti-transferrin receptor IgG3-avidin fusion protein in combination with gambogic acid against human malignant hematopoietic cells: functional relevance of iron, the receptor, and reactive oxygen species

Ortiz Sanchez, E.; Daniels, Tracy R.; Helguera, Gustavo FernandoIcon ; Martínez Maza, Otoniel; Bonavida, B.; Penichet, Manuel L.
Fecha de publicación: 12/2009
Editorial: Nature Publishing Group
Revista: Leukemia
ISSN: 0887-6924
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Ingenierías y Tecnologías

Resumen

The human transferrin receptor (hTfR) is a target for cancer immunotherapy due to its overexpression on the surface of cancer cells. We previously developed an antibody-avidin fusion protein that targets hTfR (anti-hTfR IgG3-Av) and exhibits intrinsic cytotoxicity against certain malignant cells. Gambogic acid (GA), a drug that also binds hTfR, induces cytotoxicity in several malignant cell lines. We now report that anti-hTfR IgG3-Av and GA induce cytotoxicity in a new broader panel of hematopoietic malignant cell lines. Our results show that the effect of anti-hTfR IgG3-Av is iron-dependent whereas that of GA is iron-independent in all cells tested. In addition, we observed that GA exerts a TfR-independent cytotoxicity. We also found that GA increases the generation of reactive oxygen species that may play a role in the cytotoxicity induced by this drug. Additive cytotoxicity was observed by simultaneous combination treatment with these drugs and synergy by using anti-hTfR IgG3-Av as a chemosensitizing agent. In addition, we found a concentration of GA that is toxic to malignant hematopoietic cells but not to human hematopoietic progenitor cells. Our results suggest that these two compounds may be effective, alone or in combination, for the treatment of human hematopoietic malignancies.
Palabras clave: hTfR , Gambogic Acid , Monoclonal Antibody , Chemosensitization
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
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URI: http://hdl.handle.net/11336/252140
URL: https://www.nature.com/articles/leu2008270
DOI: https://doi.org/10.1038/leu.2008.270
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Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Ortiz Sanchez, E.; Daniels, Tracy R.; Helguera, Gustavo Fernando; Martínez Maza, Otoniel; Bonavida, B.; et al.; Enhanced cytotoxicity of an anti-transferrin receptor IgG3-avidin fusion protein in combination with gambogic acid against human malignant hematopoietic cells: functional relevance of iron, the receptor, and reactive oxygen species; Nature Publishing Group; Leukemia; 23; 1; 12-2009; 59-70
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