Epigenetic targets of bioactive dietary components for cancer prevention and therapy

Abstract

The emergent interest in cancer epigenetics stems from the fact that epigenetic modifications are implicated in virtually every step of tumorigenesis. More interestingly, epigenetic changes are reversible heritable changes that are not due to the alteration in DNA sequence but have potential to alter gene expression. Dietary agents consist of many bioactive ingredients which actively regulate various molecular targets involved in tumorigenesis. We present evidence that numerous bioactive dietary components can interfere with various epigenetic targets in cancer prevention and therapy. These agents include curcumin (turmeric), genistein (soybean), tea polyphenols (green tea), resveratrol (grapes), and sulforaphane (cruciferous vegetables). These bioactive components alter the DNA methylation and histone modifications required for gene activation or silencing in cancer prevention and therapy. Bioactive components mediate epigenetic modifications associated with the induction of tumor suppressor genes such as p21WAF1/CIP1 and inhibition of tumor promoting genes such as the human telomerase reverse transcriptase during tumorigenesis processes. Here, we present considerable evidence that bioactive components and their epigenetic targets are associated with cancer prevention and therapy which should facilitate novel drug discovery and development. In addition, remarkable advances in our understanding of basic epigenetic mechanisms as well as the rapid progress that is being made in developing powerful new technologies, such as those for sensitive and quantitative detection of epigenetic and epigenomic changes in cancer biology, hold great promise for novel epigenetic approaches to cancer prevention and therapy.

Cucurbitacin B Alters the Expression of Tumor-Related Genes by Epigenetic Modifications in NSCLC and Inhibits NNK-Induced Lung Tumorigenesis

“…Interestingly, we found that CuB inhibited the expression of both DNMTs and HDACs in these cells. Previous studies have shown that treatment with either DNMTs inhibitor alone or in combination with HDACs inhibitor altered the expressions of TSGs and TPGs in many cancers (3,21,28,30). In general, promoter regions of the TSGs are hypermethylated causing their silencing in cancer and treatment with DNMTs inhibitor has been shown to reactivate their expression by altering their methylation status (28).…”

“…These compounds possess the capability to reverse the epigenetic alterations. Bioactive natural compounds have been shown to restore the expressions of to tumor suppressor genes (TSG) altered during the course of carcinogenesis (2,3). Therefore, the uses of bioactive natural compounds have been a major focus of interest as therapeutic options against various classes of diseases, including cancer.…”

“…We have previously shown that dietary combination of green tea polyphenol, a DNMT inhibitor, and sulforaphane, HDAC inhibitor reactivates estrogen receptor (ER)-a in ER-a-negative human breast cancer cells through active chromatin modifications (6). In addition, natural compounds have shown to sensitize the cancer cells for the subsequent treatment with available therapeutics (3,8). In this study, we explored the epigenetic modulatory activities of cucurbitacin B against NSCLC.…”

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

“…Among the bioactive compounds of plant origin that mediate epigenetic modifications there are agents like genistein (soybean), resveratrol (grapes), curcumin (turmeric), tea catechins (green tea), and sulforaphane (cruciferous vegetables) that have been considered in cancer prevention and therapy (Meeran et al, 2010;Li and Tollefsbol, 2010).…”

“…Other bioactive compounds have been reported to inhibit DNMTs or modify histone acetylation, including lycopene, garcinol, luteolin, butein, apigenin, silymarin, rosmarinic acid, anacardic acid or baicalein (Campion et al, 2010;Meeran et al, 2010;Park et al, 2012). Some of them could have some benefits in the treatment or prevention of metabolic disorders.…”