Document Detail

High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells.
MedLine Citation:
PMID:  17868486     Owner:  NLM     Status:  MEDLINE    
Folate, a water-soluble B vitamin, is a cofactor in one-carbon metabolism and is essential for DNA synthesis, amino acid interconversion, methylation and, consequently, normal cell growth. In animals with existing pre-neoplastic and neoplastic lesions, folic acid supplementation increases the tumour burden. To identify processes that are affected by increased folic acid levels, we compared HT29 human colon cancer cells exposed to a chronic supplemental (100 ng/ml) level of folic acid to cells exposed to a normal (10 ng/ml) level of folic acid, in the presence of vitamin B12 and other micronutrients involved in the folate-methionine cycle. In addition to higher intracellular folate levels, HT29 cells at 100 ng folic acid/ml displayed faster growth and higher metabolic activity. cDNA microarray analysis indicated an effect on cell turnover and Fe metabolism. We fully confirmed these effects at the physiological level. At 100 ng/ml, cell assays showed higher proliferation and apoptosis, while gene expression analysis and a lower E-cadherin protein expression indicated decreased differentiation. These results are in agreement with the promoting effect of folic acid supplementation on established colorectal neoplasms. The lower expression of genes related to Fe metabolism at 100 ng folic acid/ml was confirmed by lower intracellular Fe levels in the cells exposed to folic acid at 100 ng/ml. This suggests an effect of folate on Fe metabolism.
Linette Pellis; Yvonne Dommels; Dini Venema; Ab van Polanen; Esther Lips; Hakan Baykus; Frans Kok; Ellen Kampman; Jaap Keijer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-10
Journal Detail:
Title:  The British journal of nutrition     Volume:  99     ISSN:  0007-1145     ISO Abbreviation:  Br. J. Nutr.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-06     Completed Date:  2008-05-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372547     Medline TA:  Br J Nutr     Country:  England    
Other Details:
Languages:  eng     Pagination:  703-8     Citation Subset:  IM    
RIKILT-Institute of Food Safety, PO Box 230, 6700 AE Wageningen, The Netherlands.
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MeSH Terms
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Colonic Neoplasms / metabolism*,  pathology
Dietary Supplements
Epithelial Cells / drug effects,  metabolism*,  pathology
Folic Acid / pharmacology*
Gene Expression Profiling
HT29 Cells
Iron / analysis,  metabolism
Methionine / metabolism
Oligonucleotide Array Sequence Analysis
Tetrahydrofolates / metabolism
Vitamin B 12 / metabolism,  pharmacology
Vitamin B Complex / pharmacology*
Reg. No./Substance:
0/Tetrahydrofolates; 12001-76-2/Vitamin B Complex; 3432-99-3/5,10-methylenetetrahydrofolate; 59-30-3/Folic Acid; 63-68-3/Methionine; 68-19-9/Vitamin B 12; 7439-89-6/Iron

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