Epigenetic activities of flavonoids in the prevention and treatment of cancer

Abstract

Aberrant epigenetic modifications are described in an increasing number of pathological conditions, including neurodegenerative diseases, cardiovascular diseases, diabetes mellitus type 2, obesity and cancer. The general reversibility of epigenetic changes makes them an attractive and promising target e.g. in the treatment of cancer. Thus, a growing number of epigenetically active compounds are currently tested in clinical trials for their therapeutic potential. Interestingly, many phytochemicals present in plant foods, particularly flavonoids, are suggested to be able to alter epigenetic cellular mechanisms. Flavonoids are natural phenol compounds that form a large group of secondary plant metabolites with interesting biological activities. They can be categorized into six major subclasses, which display diverse properties affecting the two best characterized epigenetic mechanisms: modulation of the DNA methylation status and histone acetylation. High dietary flavonoid intake has strongly been suggested to reduce the risk of numerous cancer entities in a large body of epidemiological studies. Established health-promoting effects of diets rich in fruit and vegetables are faced by efforts to use purified flavonoids as supplements or pharmaceuticals, whereupon data on the latter applications remain controversial. The purpose of this review is to give an overview of current research on flavonoids to further elucidate their potential in cancer prevention and therapy, thereby focusing on their distinct epigenetic activities.

Novel histone deacetylase inhibitors derived from Magnolia officinalis significantly enhance TRAIL-induced apoptosis in non-small cell lung cancer

“…Thus, finding an herb-derived or plant-derived effective anti-tumor agent with low toxicity would be more promising for chemoprevention. Overwhelming evidence demonstrated that flavonoids, such as apigenin and luteolin, extracted from plants could regulate histone acetylation and subsequently inhibit PI3K, STAT3, IGF1R, and HER2 to exert biological activities [49]. Feijoa extracts were also reported to increase histone acetylation by suppressing HDACs function, ultimately resulting in the apoptosis of lymphadenoma cells [47].…”

EGCG Prevents High Fat Diet-Induced Changes in Gut Microbiota, Decreases of DNA Strand Breaks, and Changes in Expression and DNA Methylation ofDnmt1andMLH1in C57BL/6J Male Mice

“…EGCG inhibits Dnmt activity resulting in a decreased 5-methylcytosine concentration; 20  μ mol/L of EGCG already inhibited Dnmt activity in oesophageal (KYSE-150), colon (HT-29), prostate (PC-3), and breast (MCF7 and MDA-MB-231) cancer cells, although no effects of EGCG on Dnmt activity (2–50  μ mol/L) are also shown in cancer cells. Another Dnmt inhibitory pathway of flavan-3-ols results from an increase of S-adenosyl-l-homocysteine (SAH) [14]. A reduced Dnmt activity reactivates methylation-silenced genes in a dose (5–50  μ mM of EGCG) and time dependent (12–144 h) manner [25].…”

“…In contrast, ROS-induced oxidative stress contributes to hypermethylation of normally unmethylated promoter regions, resulting in transcriptional silencing of key antioxidant enzymes as well as tumor suppressor genes [7, 8]. EGCG also alters histone acetyl transferase (HAT) activity, resulting in aberrant chromatin structures, as well as miRNA expression in hepatocellular carcinoma cells [14]. …”

6- and 8-Prenylnaringenin, Novel Natural Histone Deacetylase Inhibitors Found in Hops, Exert Antitumor Activity on Melanoma Cells

“…Determination of HDACi activity was performed with HDAC assay kit (Active Motif, La Hulpe, Belgium) as described by the manufacturer with an incubation time of 2 h at 37°C, using 6-PN and 8-PN at rising concentrations (5,10,20,50 and 100 µmol/L, both from Sigma-Aldrich).…”

“…Today a variety of nutritional or dietary compounds are investigated for their potential to be epigenetically active, especially with regard to their antiproliferative properties [20]. Particularly epigenetic modulation of cellular histone proteins by histone deacetylases (HDAC) is of great interest due to the inherent antitumor activity of synthetic and natural HDAC inhibitors (HDACi).…”