title: The effects of folic acid on global DNA methylation and colonosphere formation in colon cancer cell lines.
abstract: Folate and its synthetic form, folic acid (FA), are essential vitamins for the regeneration of S-adenosyl methionine molecules, thereby maintaining adequate cellular methylation. The deregulation of DNA methylation is a contributing factor to carcinogenesis, as alterations in genetic methylation may contribute to stem cell reprogramming and dedifferentiation processes that lead to a cancer stem cell (CSC) phenotype. Here, we investigate the potential effects of FA exposure on DNA methylation and colonosphere formation in cultured human colorectal cancer (CRC) cell lines. We show for the first time that HCT116, LS174T, and SW480 cells grown without adequate FA demonstrate significantly impaired colonosphere forming ability with limited changes in CD133, CD166, and EpCAM surface expression. These differences were accompanied by concomitant changes to DNA methyltransferase (DNMT) enzyme expression and DNA methylation levels, which varied depending on cell line. Taken together, these results demonstrate an interaction between FA metabolism and CSC phenotype in vitro and help elucidate a connection between supplemental FA intake and CRC development.
authors: Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1. Electronic address: nfarias@uoguelph.ca.
authors: Nathan
authors: N
authors: Farias
authors: Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1. Electronic address: nho@uoguelph.ca.
authors: Nelson
authors: N
authors: Ho
authors: Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1. Electronic address: sbutler@uoguelph.ca.
authors: Stacey
authors: S
authors: Butler
authors: Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1. Electronic address: ldelaney@uoguelph.ca.
authors: Leanne
authors: L
authors: Delaney
authors: Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1. Electronic address: jmorris7@uoguelph.ca.
authors: Jodi
authors: J
authors: Morrison
authors: Investigative Science Inc., Burlington, ON, Canada L7T 4A8. Electronic address: sshahrzad@investigativescience.com.
authors: Siranoush
authors: S
authors: Shahrzad
authors: Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1. Electronic address: bcoomber@uoguelph.ca.
authors: Brenda L
authors: BL
authors: Coomber
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D000090205:DNA Methyltransferase 3A; D015254:DNA Modification Methylases / Q000378:metabolism; D005492:Folic Acid / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D015254:DNA Modification Methylases; D005492:Folic Acid; D012097:Repressor Proteins; D000097584:DNA Methyltransferase 3B; C411744:DMAP1 protein, human; C000717967:DNMT3A protein, human
keywords: Cancer stem cell; Colonospheres; Colorectal cancer; DNA methylation; DNMT; Folate