QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Palozza, P. Articles by Calviello, G. Search for Related Content PubMed PubMed Citation Articles by Palozza, P. Articles by Calviello, G.

---

Nutrient-Gene Interactions

ß-Carotene Regulates NF-B DNA-Binding Activity by a Redox Mechanism in Human Leukemia and Colon Adenocarcinoma Cells¹

Institute of General Pathology, Catholic University, Rome, Italy and ^* Section of Toxicology and Biomedicine, Ente per le Nuove Tecnologie, l’Energia e l’Ambiente, C.R. Casaccia, Rome, Italy

²To whom correspondence should be addressed. E-mail: p.palozza{at}rm.inicatt.it.

We demonstrated previously that ß-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)-B 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 ß-carotene, alone or in combination with -tocopherol or N-acetylcysteine, and changes in 1) cell oxidative status, 2) cell growth and apoptosis, 3) DNA-binding activity of NF-B and 4) expression of c-myc, a NF-B target gene involved in apoptosis, were evaluated. In HL-60 cells, ß-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-B and by a significant inhibition (P < 0.002) of cell growth. NF-B DNA-binding activity increased at 3 h and persisted for at least 48 h. Colon adenocarcinoma cells displayed substantial differences in their sensitivity to ß-carotene, exhibiting increased ROS levels and activation of NF-B 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, -tocopherol and N-acetylcysteine inhibited the effects of ß-carotene on NF-B, 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-B induced by ß-carotene is involved in the growth-inhibitory and proapoptotic effects of the carotenoid in tumor cells.

KEY WORDS: • ß-carotene • NF-B • redox status • cell growth • apoptosis

This article has been cited by other articles:

				O. K. Chun, S.-J. Chung, K. J. Claycombe, and W. O. Song Serum C-Reactive Protein Concentrations Are Inversely Associated with Dietary Flavonoid Intake in U.S. Adults J. Nutr., April 1, 2008; 138(4): 753 - 760. [Abstract] [Full Text] [PDF]

				N. B. Janakiram, I. Cooma, A. Mohammed, V. E. Steele, and C. V. Rao -Ionone inhibits colonic aberrant crypt foci formation in rats, suppresses cell growth, and induces retinoid X receptor-{alpha} in human colon cancer cells Mol. Cancer Ther., January 1, 2008; 7(1): 181 - 190. [Abstract] [Full Text] [PDF]

				P. Senesse, M. Touvier, E. Kesse, J. Faivre, and M.-C. Boutron-Ruault Tobacco Use and Associations of {beta}-Carotene and Vitamin Intakes with Colorectal Adenoma Risk J. Nutr., October 1, 2005; 135(10): 2468 - 2472. [Abstract] [Full Text] [PDF]

				A. Nkondjock, P. Ghadirian, K. C. Johnson, D. Krewski, and the Canadian Cancer Registries Epidemiology Resear Dietary Intake of Lycopene Is Associated with Reduced Pancreatic Cancer Risk J. Nutr., March 1, 2005; 135(3): 592 - 597. [Abstract] [Full Text] [PDF]

				J. A. Satia, T. Keku, J. A. Galanko, C. Martin, R. T. Doctolero, A. Tajima, R. S. Sandler, and J. M. Carethers Diet, Lifestyle, and Genomic Instability in the North Carolina Colon Cancer Study Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 429 - 436. [Abstract] [Full Text] [PDF]

				X. Gao, O. I. Bermudez, and K. L. Tucker Plasma C-Reactive Protein and Homocysteine Concentrations Are Related to Frequent Fruit and Vegetable Intake in Hispanic and Non-Hispanic White Elders J. Nutr., April 1, 2004; 134(4): 913 - 918. [Abstract] [Full Text] [PDF]