Por favor, use este identificador para citar o enlazar este ítem: 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: pdf
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
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