Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
Curr Issues Mol Biol ; 46(1): 450-460, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38248330

RESUMEN

Developing strategies for the radiosensitization of cancer cells by the inhibition of genes, which harbor low toxicity to normal cells, will be useful for improving cancer radiotherapy. Here, we focused on a ß-site of amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1; ß-secretase, memapsin-2). By functional inhibition of this peptidase by siRNA, it has also recently been shown that the DNA strand break marker, γH2AX foci, increased, suggesting its involvement in DNA damage response. To investigate this possibility, we knocked down BACE1 with siRNA in cancer cell lines, and sensitization to γ-irradiation was examined by a colony formation assay, γH2AX foci and level analysis, and flow cytometry. BACE1 knockdown resulted in the sensitization of HeLa, MDA-MB-231, U2OS, and SAOS cells to γ-irradiation in a diverse range. BACE1 knockdown showed a weak radiosensitization effect in osteosarcoma U2OS cells, which has a normal p53 function. HeLa and SAOS cells, which harbor p53 dysfunction, exhibited a greater level of radiosensitization. These results suggest that BACE1 may be a potential target for the radiosensitization in particular cancer cells.

2.
Int J Mol Sci ; 23(9)2022 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-35563460

RESUMEN

The radiosensitization of tumor cells is one of the promising approaches for enhancing radiation damage to cancer cells and limiting radiation effects on normal tissue. In this study, we performed a comprehensive screening of radiosensitization targets in human lung cancer cell line A549 using an shRNA library and identified apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G: A3G) as a candidate target. APOBEC3G is an innate restriction factor that inhibits HIV-1 infection as a cytidine deaminase. APOBEC3G knockdown with siRNA showed an increased radiosensitivity in several cancer cell lines, including pancreatic cancer MIAPaCa2 cells and lung cancer A549 cells. Cell cycle analysis revealed that APOBEC3G knockdown increased S-phase arrest in MIAPaCa2 and G2/M arrest in A549 cells after γ-irradiation. DNA double-strand break marker γH2AX level was increased in APOBEC3G-knocked-down MIAPaCa2 cells after γ-irradiation. Using a xenograft model of A549 in mice, enhanced radiosensitivity by a combination of X-ray irradiation and APOBEC3G knockdown was observed. These results suggest that the functional inhibition of APOBEC3G sensitizes cancer cells to radiation by attenuating the activation of the DNA repair pathway, suggesting that APOBEC3G could be useful as a target for the radiosensitization of cancer therapy.


Asunto(s)
Desaminasa APOBEC-3G , Rayos gamma , Tolerancia a Radiación , Desaminasa APOBEC-3G/antagonistas & inhibidores , Desaminasa APOBEC-3G/farmacología , Animales , Apoptosis , Línea Celular Tumoral , Citidina Desaminasa/genética , Citidina Desaminasa/metabolismo , Puntos de Control de la Fase G2 del Ciclo Celular , Rayos gamma/uso terapéutico , Humanos , Neoplasias Pulmonares/radioterapia , Ratones , Tolerancia a Radiación/genética , Tolerancia a Radiación/fisiología
3.
Sci Rep ; 5: 18231, 2015 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-26667181

RESUMEN

A comprehensive genome-wide screen of radiosensitization targets in HeLa cells was performed using a shRNA-library/functional cluster analysis and DNMT3B was identified as a candidate target. DNMT3B RNAi increased the sensitivity of HeLa, A549 and HCT116 cells to both γ-irradiation and carbon-ion beam irradiation. DNMT3B RNAi reduced the activation of DNA damage responses induced by γ-irradiation, including HP1ß-, γH2AX- and Rad51-foci formation. DNMT3B RNAi impaired damage-dependent H2AX accumulation and showed a reduced level of γH2AX induction after γ-irradiation. DNMT3B interacted with HP1ß in non-irradiated conditions, whereas irradiation abrogated the DNMT3B/HP1ß complex but induced interaction between DNMT3B and H2AX. Consistent with radiosensitization, TP63, BAX, PUMA and NOXA expression was induced after γ-irradiation in DNMT3B knockdown cells. Together with the observation that H2AX overexpression canceled radiosensitization by DNMT3B RNAi, these results suggest that DNMT3B RNAi induced radiosensitization through impairment of damage-dependent HP1ß foci formation and efficient γH2AX-induction mechanisms including H2AX accumulation. Enhanced radiosensitivity by DNMT3B RNAi was also observed in a tumor xenograft model. Taken together, the current study implies that comprehensive screening accompanied by a cluster analysis enabled the identification of radiosensitization targets. Downregulation of DNMT3B, one of the targets identified using this method, radiosensitizes cancer cells by disturbing multiple DNA damage responses.


Asunto(s)
ADN (Citosina-5-)-Metiltransferasas/genética , Daño del ADN , Metilación de ADN , Regulación de la Expresión Génica , Tolerancia a Radiación/genética , Animales , Puntos de Control del Ciclo Celular/genética , Puntos de Control del Ciclo Celular/efectos de la radiación , Línea Celular Tumoral , Supervivencia Celular/genética , Supervivencia Celular/efectos de la radiación , Homólogo de la Proteína Chromobox 5 , Proteínas Cromosómicas no Histona/genética , Análisis por Conglomerados , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Modelos Animales de Enfermedad , Rayos gamma , Perfilación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Redes Reguladoras de Genes , Células HeLa , Histonas/metabolismo , Humanos , Masculino , Ratones , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/radioterapia , Unión Proteica , ARN Interferente Pequeño/genética , Transducción de Señal/efectos de la radiación , Ensayos Antitumor por Modelo de Xenoinjerto , ADN Metiltransferasa 3B
4.
Appl Radiat Isot ; 106: 213-9, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26302661

RESUMEN

To understand the mechanism of cell death induced by boron neutron capture reaction (BNCR), we performed proteome analyses of human squamous tumor SAS cells after BNCR. Cells were irradiated with thermal neutron beam at KUR after incubation under boronophenylalanine (BPA)(+) and BPA(-) conditions. BNCR mainly induced typical apoptosis in SAS cells 24h post-irradiation. Proteomic analysis in SAS cells suggested that proteins functioning in endoplasmic reticulum, DNA repair, and RNA processing showed dynamic changes at early phase after BNCR and could be involved in the regulation of cellular response to BNCR. We found that the BNCR induces fragments of endoplasmic reticulum-localized lymphoid-restricted protein (LRMP). The fragmentation of LRMP was also observed in the rat tumor graft model 20 hours after BNCT treatment carried out at the National Nuclear Center of the Republic of Kazakhstan. These data suggest that dynamic changes of LRMP could be involved during cellular response to BNCR.


Asunto(s)
Apoptosis/efectos de la radiación , Terapia por Captura de Neutrón de Boro , Carcinoma de Células Escamosas/radioterapia , Neoplasias de la Boca/radioterapia , Proteínas de Neoplasias/metabolismo , Proteómica , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Humanos , Neoplasias de la Boca/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...