Chemopreventive Activity of Ellagitannins from (Pax) Komarov Leaves on Prostate Cancer Cells.

Several studies have shown that compounds from (Pax) Komarov leaves (APL) display potent anti-oxidative, anti-inflammatory, and anti-proliferative activities. Prostate cancer (PCa) is the most common cancer among older men, and DNA methylation is associated with PCa progression. This study aimed to investigate the chemopreventive activities of the compounds which were isolated from APL on prostate cancer cells and elucidate the mechanisms of these compounds in relation to DNA methylation. One novel ellagitannin [komaniin ()] and thirteen other known compounds, including glucose derivatives [ethyl-β-D-glucopyranose () and (4R)-p-menth-1-ene-7,8-diol 7-O-β-D-glucopyranoside ()], one phenylpropanoid [junipetrioloside A ()], three phenolic acid derivatives [ellagic acid-4-β-D-xylopyranoside (), 4-O-galloyl-quinic acid (), and gallic acid ()], two flavonoids [quercetin () and kaempferol ()], and five hydrolysable tannins [geraniin (), punicafolin (), granatin B (), 1,2,3,4,6-penta-galloyl-β-D-glucopyranoside (), and mallotusinic acid ()] were isolated from APL. The hydrolyzable tannins (, , , , , and ) showed potent anti-PCa proliferative and apoptosis-promoting activities. Among the compounds, the ellagitannins in the dehydrohexahydroxydiphenoyl (DHHDP) group (, , , and ), the novel compound showed the most potent inhibitory activity on DNA methyltransferase (DNMT1, 3a and 3b) and glutathione S-transferase P1 methyl removing and re-expression activities. Thus, our results suggested that the ellagitannins (, , , and isolated from APL could be a promising treatment option for PCa.