THE ROLE OF PLANT COMPONENTS ON ABBERANT DNA METHYLATION IN CANCER

Numerous pathways are deregulated in cancer cells including genetic and epigenetic events. One of the major epigenetic mechanisms is DNA methylation which is catalyzed by DNA methyltransferase (DNMT) enzymes. In normal cells, cytosine in CpG islands of most genes are maintained unmethylated, allowing them to be transcript. While DNA hypermethylation in promoter of tumor suppressor genes causes their transcriptional silencing that play significant role in cancer development and progression. Several plant components have the ability to prevent and treatment cancer. Among different mechanism of action, some of these bioactive factors could reverse aberrant DNA methylation in cancer cells. This abstract aimed to summarizes the main anticancer plant components which can act on methylase enzyme and modify DNA methylation. Epigallocatechin-3-gallate, mainly in green tea, inhibits DNMT activity and reactivates p16, RARβ, MGMT, hMLH2, GSTP genes in esophageal, colon, prostate, and breast cancer. Curcumin, a yellow polyphenol from the rhizomes of Curcuma longa, inhibits DNMT1 activity and reverses hypermethylation of NEUROG1 and NRF1 genes. Resveratrol (3,5,4’- trihydroxystilbene), a natural phytoalexin in several plants, such as grapes, berries, plums, and peanuts, can modify altered methylation of BRCA1, DNMTs, and MBD2 genes. Flavonoids such as quercetin, fisetin, and myricetin, inhibit DNMT activity in different cancers. Genistin, a isoflavones from soybeans, could alter hypermethylation of p16INK4A, RARβ, MGMT, phosphatase and tensin homolog (PTEN), cylindromatosis (Turban tumor syndrome, CYLD), 381 / 864 GSTP1, EPHB2, and BTG3 in esophageal and prostate cancer. Phenethyl isothiocyanate (PITC) in myeloma cells can induce DNA demethylation of p16 gene. sulforaphane, widely present in broccoli, sprouts, cabbage and kale, and lycopene from tomatoes, and quercetin from citrus fruits and buck wheat have also ability to reverse DNA methylation. Many bioactive components in plants have been demonstrated to have cancer prevention and treatment properties through reversing the DNA methylation. Therefore, these dietary components as epigenetically therapeutic agents could become an attractive new approach for cancer prevention and intervention at the moment.