β-Carotene Regulates NF-κB DNA-Binding Activity by a Redox Mechanism in Human Leukemia and Colon Adenocarcinoma Cells
Open Access
- 1 February 2003
- journal article
- research article
- Published by Elsevier BV in Journal of Nutrition
- Vol. 133 (2), 381-388
- https://doi.org/10.1093/jn/133.2.381
Abstract
We demonstrated previously that β-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)-κB 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 β-carotene, alone or in combination with α-tocopherol or N-acetylcysteine, and changes in 1) cell oxidative status, 2) cell growth and apoptosis, 3) DNA-binding activity of NF-κB and 4) expression of c-myc, a NF-κB target gene involved in apoptosis, were evaluated. In HL-60 cells, β-carotene induced a significant increase in reactive oxygen species (ROS) production (P < 0.001) and in oxidized glutathione (GSSG) content (P < 0.005) at concentrations ≥10 μmol/L. These effects were always accompanied by a sustained elevation of NF-κB and by a significant inhibition (P < 0.002) of cell growth. NF-κB DNA-binding activity increased at 3 h and persisted for at least 48 h. Colon adenocarcinoma cells displayed substantial differences in their sensitivity to β-carotene, exhibiting increased ROS levels and activation of NF-κB at concentrations much lower in LS-174 cells (2.5–5.0 μmol/L) than in WiDr cells (50–100 μmol/L). In all cell lines studied, α-tocopherol and N-acetylcysteine inhibited the effects of β-carotene on NF-κB, 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-κB induced by β-carotene is involved in the growth-inhibitory and proapoptotic effects of the carotenoid in tumor cells.Keywords
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