The effects of folic acid on global DNA methylation and colonosphere formation in colon cancer cell lines

Farias, Nathan; Ho, Nelson; Butler, Stacey J.; Delaney, Leanne M.; Morrison, Jodi; Shahrzad, Siranoush; Coomber, Brenda L.

doi:10.1016/j.jnutbio.2015.02.002

Cited by 60 publications

(37 citation statements)

References 62 publications

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“…In addition, there is evidence that nutritional stimuli can modify epigenetic mechanisms, such as DNA methylation. 9 DNA methylation/demethylation plays a crucial role in gene regulation and could also be responsible for the presentation of senescence. For example, being fed a chronic HF diet mice (from weaning to >15 weeks of age) altered the patterns of DNA methylation in the brain, 10 and the OS and inflammation that increase by HF diet are thought to be important contributors of DNA hypermethylation.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Stress Induces Cognitive Disturbances and Inflammation in Aged Mice: Protective Role of Resveratrol

Palomera-Ávalos

Griñán-Ferré

Izquierdo

et al. 2017

Rejuvenation Research

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Inflammation and oxidative stress (OS) are key points in age progression. Both processes impact negatively in cognition and in brain functions. Resveratrol (RV) has been postulated as a potent antioxidant natural compound, with rejuvenating properties. Inducing a metabolic stress by high-fat (HF) diet in aged C56/BL6 (24 months) led to cognitive disturbances compared with control age mated and with young mice. These changes were prevented by RV. Molecular determinations demonstrated a significant increase in some inflammatory parameters (TNF-a, Cxcl10, IL-1, IL-6, and Ccl3) in old mice, but slight changes in OS machinery. RV mainly induced the recovery of the metabolically stressed animals. The study of key markers involved in senescence and rejuvenation (mitochondrial biogenesis and Sirt1-AMPK-PGC1-a) demonstrated that RV is also able to modulate the changes in these cellular metabolic pathways. Moreover, changes of epigenetic marks (methylation and acetylation) that are depending on OS were demonstrated. On the whole, results showed the importance of integrative role of different cellular mechanisms in the deleterious effects of age in cognition and the beneficial role of RV. The work presented in this study showed a wide range of processes modified in old age and by metabolic stress, weighting the importance of each one and the role of RV as a possible strategy for fighting against.

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Section: Introductionmentioning

confidence: 99%

Metabolic Stress Induces Cognitive Disturbances and Inflammation in Aged Mice: Protective Role of Resveratrol

Palomera-Ávalos

Griñán-Ferré

Izquierdo

et al. 2017

Rejuvenation Research

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“…In addition, dietary intake and blood level of folate appear to be negatively correlated to the risk of tumorigenesis in several organs, such as the breast, colon, and lung (10)(11)(12). Recently, a number of studies have reported that high folate supplementation might cause epigenetic changes that may promote carcinogenesis (13)(14)(15)(16)(17). However, little was done about the antimutagenic effects of folate supplementation.…”

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confidence: 99%

Folic Acid Supplementation Reduces the Mutagenicity and Genotoxicity Caused by Benzo(a)pyrene

Zhang

Zhan

et al. 2016

J Nutr Sci Vitaminol

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Summary Folate is a vital vitamin for the human being and its defi ciency can lead to a variety of clinical abnormalities ranging from neural tube defects to cancers. Benzo(a)pyrene (BaP), a strong mutagen and carcinogen, is considered one of the common contaminants in food. The aim of this study was to investigate the positive effect of folate on cancer prevention at a fundamental level. In the present study, we investigated the impact of folic acid on BaP-induced mutagenicity and genotoxicity by means of in vitro and in vivo experiments. The reformed Ames test was applied to study the antimutagenicity of folic acid against BaP. The protective effect of folic acid on cytotoxicity caused by BaP in human liver cell line L02 was evaluated by MTT assay. In addition, the effect of folic acid on the BaP-induced genotoxicity in vivo was assessed by mouse bone marrow micronucleus assay. The results indicated that folic acid signifi cantly inhibited the reverse mutation of Salmonella typhimurium strains TA98 and TA100, and protected the viability of human liver cells against BaP (pϽ0.01). The micronucleus test showed that all doses of folic acid had a remarkable protective effect for the female mice (pϽ0.01). In conclusion, folic acid was found to reduce the mutagenicity and genotoxicity induced by BaP.

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“…In vitro studies on colon cancer cell lines showed that folic acid supplementation in medium is capable of changing DNA methylation patterns, as well as altering the proliferative capacity and phenotype of these cells in culture. This is of particular importance in understanding the role of folic acid supplementation on the behaviour of tumours in terms of phenotypic changes, motility and invasion [144]. Other studies have reported an increased proliferation due to altered DNA methylation in response to excessive folic acid supplementation [6, 145].…”

Section: Folates and Cancermentioning

confidence: 99%

Folate deficiency as predisposing factor for childhood leukaemia: a review of the literature

et al. 2017

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BackgroundFolic acid and its derivates, known as folates, are chemoprotective micronutrients of great interest because of their essential role in the maintenance of health and genomic integrity. The supplementation of folic acid during pregnancy has long been known to reduce the risk of neural tube defects (NTDs) in the foetus. Folate metabolism can be altered by many factors, including adequate intake through diet. Folate deficiency can compromise the synthesis, repair and methylation of DNA, with deleterious consequences on genomic stability and gene expression. These processes are known to be altered in chronic diseases, including cancer and cardiovascular diseases.Main bodyThis review focuses on the association between folate intake and the risk of childhood leukaemia. Having compiled and analysed studies from the literature, we show the documented effects of folates on the genome and their role in cancer prevention and progression with particular emphasis on DNA methylation modifications. These changes are of crucial importance during pregnancy, as maternal diet has a profound impact on the metabolic and physiological functions of the foetus and the susceptibility to disease in later life. Folate deficiency is capable of modifying the methylation status of certain genes at birth in both animals and humans, with potential pathogenic and tumorigenic effects on the progeny. Pre-existing genetic polymorphisms can modify the metabolic network of folates and influence the risk of cancer, including childhood leukaemias. The protective effects of folic acid might be dose dependent, as excessive folic acid could have the adverse effect of nourishing certain types of tumours.ConclusionOverall, maternal folic acid supplementation before and during pregnancy seems to confer protection against the risk of childhood leukaemia in the offspring. The optimal folic acid requirements and supplementation doses need to be established, especially in conjunction with other vitamins in order to determine the most successful combinations of nutrients to maintain genomic health and wellbeing. Further research is therefore needed to uncover the role of maternal diet as a whole, as it represents a main factor capable of inducing permanent changes in the foetus.

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The effects of folic acid on global DNA methylation and colonosphere formation in colon cancer cell lines

Cited by 60 publications

References 62 publications

Metabolic Stress Induces Cognitive Disturbances and Inflammation in Aged Mice: Protective Role of Resveratrol

Metabolic Stress Induces Cognitive Disturbances and Inflammation in Aged Mice: Protective Role of Resveratrol

Folic Acid Supplementation Reduces the Mutagenicity and Genotoxicity Caused by Benzo(a)pyrene

Folate deficiency as predisposing factor for childhood leukaemia: a review of the literature

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