Antiproliferative, apoptosis-inducing, and GSTP1 demethylation activities of Ellagitannins isolated from Cornus alba L.

This study aimed to prove the prostate cancer chemopreventive activity of compounds isolated from CA. We evaluated these compounds using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and evaluated their NF-κB inhibitory activity and apoptosis-inducing activity using western blot analysis and flow cytometry, respectively. Their DNA methylation activity was also evaluated via a methylation-specific polymerase chain reaction in androgen-dependent (LNCaP) and androgen-independent (PC-3) prostate cancer cell lines. Camptothin B (1), cornusiin B (2), and cornusiin A (3), which were isolated in our previous work, relatively reduced the protein expression levels in PCa cells. Among them, cornusiin B (2) exhibited excellent NF-κB inhibitory activity. Also, concentration-dependently increased the unmethylated DNA content and decreased the methylated DNA content in both PC-3 and LNCaP cells. Therefore, cornusiin B (2), which was isolated from CA, has the potential to act as a chemopreventive agent for prostate cancer.

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

Several studies have shown that compounds from Acer pseudosieboldianum (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 (14)] and thirteen other known compounds, including glucose derivatives [ethyl-ß-D-glucopyranose (3) and (4R)-p-menth-1-ene-7,8-diol 7-O-ß-D-glucopyranoside (4)], one phenylpropanoid [junipetrioloside A (5)], three phenolic acid derivatives [ellagic acid-4-ß-D-xylopyranoside (1), 4-O-galloyl-quinic acid (2), and gallic acid (8)], two flavonoids [quercetin (11) and kaempferol (12)], and five hydrolysable tannins [geraniin (6), punicafolin (7), granatin B (9), 1,2,3,4,6-penta-galloyl-ß-D-glucopyranoside (10), and mallotusinic acid (13)] were isolated from APL. The hydrolyzable tannins (6, 7, 9, 10, 13, and 14) showed potent anti-PCa proliferative and apoptosis-promoting activities. Among the compounds, the ellagitannins in the dehydrohexahydroxydiphenoyl (DHHDP) group (6, 9, 13, and 14), the novel compound 14 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 (6, 9, 13, and 14) isolated from APL could be a promising treatment option for PCa.