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http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/2367| Título : | Effects of 2-methoxyestradiol on apoptosis and HIF-1α and HIF-2α expression in lung cancer cells under normoxia and hypoxia. |
| Creador: | Aquino Gálvez, Arnoldo |
| Nivel de acceso: | Open access |
| Palabras clave : | Apoptosis - Efectos de drogas Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico - genética Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico - metabolismo Hipoxia de la Célula - Efectos de drogas Línea Celular Tumoral Núcleo Celular - Efectos de drogas Proliferación Celular - Efectos de drogas Estradiol - análogos & derivados Estradiol - farmacología Regulación Neoplásica de la Expresión Génica - Efectos de drogas Humanos Subunidad alfa del Factor 1 Inducible por Hipoxia - genética Subunidad alfa del Factor 1 Inducible por Hipoxia - metabolismo Neoplasias Pulmonares - tratamiento farmacológico Neoplasias Pulmonares - genética Neoplasias Pulmonares - metabolismo Apoptosis - drug effects Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Cell Hypoxia - drug effects Cell Line, Tumor Cell Nucleus - drug effects Cell Proliferation - drug effects Estradiol - analogs & derivatives Estradiol - pharmacology Gene Expression Regulation, Neoplastic - drug effects Humans Hypoxia- Inducible Factor 1, alpha Subunit - genetics Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - metabolism Apoptosis Cáncer HIF-1α HIF-2α 2- metoxiestradiol Hipoxia apoptosis cancer HIF-1α HIF-2α 2-methoxyestradiol hypoxia |
| Descripción : | Hypoxic tumor cells are known to be more resistant to conventional chemotherapy and radiation than normoxic cells. However, the effects of 2-methoxyestradiol (2-ME), an anti-angiogenic, antiproliferative and pro-apoptotic drug, on hypoxic lung cancer cells are unknown. The aim of the present study was to compare the effects of 2-ME on cell growth, apoptosis, hypoxia-inducible factor 1α (HIF-1α) and HIF-2α gene and protein expression in A549 cells under normoxic and hypoxic conditions. To establish the optimal 2-ME concentration with which to carry out the apoptosis assay and to examine mRNA and protein expression of HIFs, cell growth analysis was carried out through N-hexa-methylpararosaniline staining assays in A549 cell cultures treated with one of five different 2-ME concentrations at different times under normoxic or hypoxic growth conditions. The 2-ME concentration of 10 mM at 72 h was selected to perform all further experiments. Apoptotic cells were analyzed by flow cytometry. Western blotting was used to determine HIF-1α and HIF-2α protein expression in total cell extracts. Cellular localization of HIF-1α and HIF-2α was assessed by immunocytochemistry. HIF-1α and HIF-2α gene expression was determined by real-time PCR. A significant increase in the percentage of apoptosis was observed when cells were treated with 2-ME under a normoxic but not under hypoxic conditions (p=0.006). HIF-1α and HIF-2α protein expression levels were significantly decreased in cells cultured under hypoxic conditions and treated with 2-ME (p<0.001). Furthermore, 2-ME decreased the HIF-1α and HIF-2α nuclear staining in cells cultured under hypoxia. The HIF-1α and HIF-2α mRNA levels were significantly lower when cells were exposed to 2-ME under normoxia and hypoxia. Our results suggest that 2-ME could have beneficial results when used with conventional chemotherapy in an attempt to lower the invasive and metastatic processes during cancer development due to its effects on the gene expression and protein synthesis of HIFs. |
| Colaborador(es) u otros Autores: | González-Ávila Georgina Delgado-Tello Javier Castillejos-López Manuel Mendoza-Milla Criselda Zúñiga Joaquín Checa Marco Maldonado-Martínez Héctor Aquiles Trinidad-López Axel Cisneros José Torres-Espíndola Luz María Hernández-Jiménez Claudia Sommer Bettina Cabello-Gutiérrez Carlos And Gutiérrez-González Luis H. |
| Fecha de publicación : | 2016 |
| Tipo de publicación: | Artículo |
| Formato: | |
| Identificador del Recurso : | 10.3892/or.2015.4399 |
| Fuente: | Oncology Reports 35(1):577 - 583 |
| URI : | http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/2367 |
| Idioma: | eng |
| Aparece en las colecciones: | Artículos |
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