β-Carotene Regulates NF-κB DNA-Binding Activity by a Redox Mechanism in Human Leukemia and Colon Adenocarcinoma Cells
| Autor: | Angela Torsello, Elisabetta Piccioni, Claudio Pioli, Gabriella Calviello, Vanessa Ubaldi, Fiorella Di Nicuolo, Simona Serini, Federica I. Wolf, Paola Palozza |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Programmed cell death
Cell Genes myc Medicine (miscellaneous) Apoptosis HL-60 Cells Adenocarcinoma Biology medicine Humans Transcription factor chemistry.chemical_classification Reactive oxygen species Nutrition and Dietetics Cell growth NF-kappa B Biological activity beta Carotene Molecular biology Acetylcysteine medicine.anatomical_structure chemistry Biochemistry Cell culture Colonic Neoplasms Reactive Oxygen Species Oxidation-Reduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0022-3166 |
| Popis: | We demonstrated previously that beta-carotene may affect cell growth by a redox mechanism. The purpose of this study was to determine whether the redox-sensitive transcription factor nuclear factor (NF)-kappaB may be involved in the growth-inhibitory and proapoptotic effects of the carotenoid. To test this hypothesis, human leukemic cells (HL-60) and colon adenocarcinoma cells (LS-174 and WiDr) were treated with beta-carotene, alone or in combination with alpha-tocopherol or N-acetylcysteine, and changes in 1) cell oxidative status, 2) cell growth and apoptosis, 3) DNA-binding activity of NF-kappaB and 4) expression of c-myc, a NF-kappaB target gene involved in apoptosis, were evaluated. In HL-60 cells, beta-carotene induced a significant increase in reactive oxygen species (ROS) production (P0.001) and in oxidized glutathione (GSSG) content (P0.005) at concentrations/=10 micro mol/L. These effects were always accompanied by a sustained elevation of NF-kappaB and by a significant inhibition (P0.002) of cell growth. NF-kappaB DNA-binding activity increased at 3 h and persisted for at least 48 h. Colon adenocarcinoma cells displayed substantial differences in their sensitivity to beta-carotene, exhibiting increased ROS levels and activation of NF-kappaB at concentrations much lower in LS-174 cells (2.5-5.0 micro mol/L) than in WiDr cells (50-100 micro mol/L). In all cell lines studied, alpha-tocopherol and N-acetylcysteine inhibited the effects of beta-carotene on NF-kappaB, cell growth and apoptosis, and normalized the increased expression of c-myc induced by the carotenoid. These data suggest that the redox regulation of NF-kappaB induced by beta-carotene is involved in the growth-inhibitory and proapoptotic effects of the carotenoid in tumor cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|