Other dietary compounds affecting the epigenome

Other dietary compounds affecting the epigenome

In trials designed to test Se in nonmelanoma skin cancers, 1312 individuals at a high risk of developing this disease were given either 200 μg of Se or placebo orally per day for an average of 4.5 years [193,194]. This trial did not prevent skin cancer but did produce a significant 44% secondary decrease in lung cancer incidence [193]. Se has been linked to DNA methylation in cellular and animal models and Xiang et al. found that Se treatments caused partial promoter DNA demethylation and re-expression of GSTP1 in prostate cancer cells. This study also demonstrated that Se decreased histone deacetylase activity (Figure 3 & Table 1) and increased levels of acetylated H3K9, and decreased levels of methylated H3K9 [191]. In animal studies rats fed with selenium-rich diets induced significant DNA hypomethylation in the liver and colon [195,196]. Furthermore, Se deficiency has been demonstrated to cause global hypomethylation and promoter methylation of the p16 and p53 tumor suppressor genes [197]. Se can also decrease DNMT1 protein expression and inhibit DNMT1 (Figure 1 & Table 1) by direct interaction and indirectly by influencing homocysteine concentrations [198]. In addition, investigations have demonstrated that treatment of prostate cancer cells with selenite, an inorganic form of Se, can restore the expression of anticancer genes silenced by hypermethylation suggesting that epigenetic regulation by Se may play a role in cancer prevention [191]. Although these studies are intriguing, further studies involving the epigenetic influence of selenium are needed to fully appreciate the impact of selenium on the epigenome.

Garlic (Allium sativum) has been used for the prevention of disease for many years, and is thought to have antibacterial, antiviral and anti-inflammatory activities [199]. Garlic cloves contain several compounds including: vitamins A, B-complex, C, E, fiber, free amino acids, sulfur/organosulfur compounds and proteins. In addition, garlic also contains small amounts of selenium that may contribute to its chemopreventive properties. Garlic extracts and compounds have been used in experiments involving cancer treatment and prevention in isolated cell systems and in in vivo models [199]. These studies have shown that garlic acts to inhibit cell cycle progression, induce apoptosis, inhibit angiogenesis and modifies histones [200]. Studies conducted by Nian et al. revealed that garlic organosulfur compound, allyl mercaptan, inhibits histone deacetylase (Figure 3 & Table 1) and enhances Sp3 binding on the P21/WAF1 promoter, which results in elevated p21 protein expression and cell cycle arrest [200,201]. In addition, investigations conducted by Lea et al. demonstrate the induction of histone acetylation in cancer cells treated with garlic compounds [202,203].

Folic acid, or folate, is a B vitamin found in many beans, grains, fortified breakfast cereals, pastas and green vegetables. Folate is a key element in the methyl-metabolism pathway. Dietary methyl deficiency can alter hepatic DNA methylation patterns and induce liver cancer (Table 1) [70,71]. While folate has been studied extensively for its developmental effects, folate deficiencies lead to hypomethylated genomic DNA, which is associated with tumorigenesis [204,205]. Folate deficiencies are reported to contribute to the development of several different cancers including: breast, cervix, ovary, brain, lung and colorectal [206–208]. Folate regulates the biosynthesis, repair and methylation of DNA, whereas deficiencies in folate can induce carcinogenesis by augmenting these processes [207]. In addition, studies involving colorectal cancer indicated that folate deficiency can alter cytosine methylation in DNA leading to the activation of c-Myc, a known oncogene [209,210].

While most natural dietary products have shown beneficial effects on the epigenome, not all dietary components share this characteristic. In fact, alcohol consumption is associated with harmful epigenetic modifications as well as the development/progression of several human cancers. For example, colorectal cancer patients with high alcohol consumption had aprevalence of promoter hypermethylation of numerous genes when compared with patients with low alcohol consumption (Table 1) [211,212]. In addition, studies involving head and neck cancers demonstrated that promoter hypermethylation of MGMT and WNT pathway regulators occurred more frequently in heavy and light drinkers than in nondrinkers [213].

Other dietary factors including those found in coffee, cashews, tomatoes, parsley, milk thistle and rosemary, have also been reported to have epigenetic targets all of which could not be mentioned in this article. However, bioactive components of these nutrients may be of considerable interest and may have epigenetic targets in cancer [123,214–217].