An analysis of the nature of food drugs and their role in the epigenetic settings of RNAs and miRNAs

A nutraceutical is a pharmaceutical alternative which claims physiological benefits. In the US,nutraceuticals are largely unregulated, as they exist in the same category as dietary supplements andfood additives by the FDA, under the authority of the Federal Food, Drug, and Cosmetic Act. The word"nutraceutical" is a portmanteau term, blending the words "nutrition" and "pharmaceutical". In theUnited States, the Dietary Supplement Health and Education Act (DSHEA) of 1994 defined the term"dietary supplement": “A dietary supplement is a product taken by mouth that contains a 'dietaryingredient' intended to supplement the diet. The 'dietary ingredients' in these products may include:vitamins, minerals, herbs or other botanicals, amino acids, and substances such as enzymes, organtissues, glandulars, and metabolites. Dietary supplements can also be extracts or concentrates, and maybe found in many forms such as tablets, capsules, softgels, gelcaps, liquids, or powders.” Dietarysupplements do not have to be approved by the U.S. Food and Drug Administration (FDA) beforemarketing, but companies must register their manufacturing facilities with the FDA and follow currentgood manufacturing practices (cGMPs). With a few well-defined exceptions, dietary supplements mayonly be marketed to support the structure or function of the body, and may not claim to treat a diseaseor condition, and must include a label that says: “These statements have not been evaluated by the Foodand Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.”The exceptions are when the FDA has reviewed and approved a health claim. In those situations theFDA also stipulates the exact wording allowed. Both genetic alterations and epigenetic regulations ofgenes could lead to the development of human cancers. However, recent studies have shown thatepigenetic alteration contributes signifi cantly not only to the development of cancer but also responsiblefor the progression of cancer to metastatic disease. The epigenetic regulations of specifi c genes inhuman cancer cells include DNA methylation, acetylation, histone modifi cation, nucleosomeremodeling, and small non-coding RNA regulation including the regulation of microRNAs (miRNAs).Among many epigenetic regulations, DNA methylation is the most common event and has been wellstudied for understanding the mechanisms of epigenetic regulation of genes. The DNAhypermethylation occurs in the promoter sequences of tumor suppressor gene or tumor suppressivemiRNAs leading to the down-regulation in the expression of tumor suppressor mRNAs or miRNAs,resulting in the development and progression of various cancers. Interestingly, recent studies haveshown that several non- toxic natural agents known as nutraceuticals including isofl avone, curcumin,epigallocatechin-3-gallate, resveratrol, indole-3-carbinol, 3,3′-diindolylmethane, and lycopene coulddemethylate DNA at their hypermethylation sites or modulate histone, demonstrating their potentialroles in the epigenetic regulation of mRNAs and miRNAs. These epigenetic regulations of mRNAs andmiRNAs could be one of the molecular mechanisms by which nutraceuticals inhibit carcinogenesis andcancer progression, and thus either nutraceuticals or their synthetic analogs could serve as noveldemethylating agents for the treatment of human malignancies.

An analysis of the nature of food drugs and their role in the epigenetic settings of RNAs and miRNAs Keywords:

DNA methylation , Acetylation , Tumor suppressor gene , Tumor suppressive miRNA.