Farias Nathan, Ho Nelson, Butler Stacey, Delaney Leanne, Morrison Jodi, Shahrzad Siranoush, Coomber Brenda L
Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1.
Investigative Science Inc., Burlington, ON, Canada L7T 4A8.
J Nutr Biochem. 2015 Aug;26(8):818-26. doi: 10.1016/j.jnutbio.2015.02.002. Epub 2015 Mar 13.
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.
叶酸及其合成形式叶酸（FA）是S-腺苷甲硫氨酸分子再生所必需的维生素，从而维持足够的细胞甲基化。DNA甲基化失调是致癌作用的一个促成因素，因为基因甲基化的改变可能有助于干细胞重编程和去分化过程，从而导致癌症干细胞（CSC）表型。在此，我们研究了FA暴露对培养的人结肠直肠癌（CRC）细胞系中DNA甲基化和结肠球形成的潜在影响。我们首次表明，在没有足够FA的情况下生长的HCT116、LS174T和SW480细胞显示出明显受损的结肠球形成能力，而CD133、CD166和EpCAM表面表达的变化有限。这些差异伴随着DNA甲基转移酶（DNMT）酶表达和DNA甲基化水平的相应变化，这些变化因细胞系而异。综上所述，这些结果证明了体外FA代谢与CSC表型之间的相互作用，并有助于阐明补充FA摄入与CRC发展之间的联系。
