title: Antiproliferative Effects of New Dimeric Ellagitannin from Cornus alba in Prostate Cancer Cells Including Apoptosis-Related S-Phase Arrest.
abstract: Activity-guided isolation of 80% acetone extract of Cornus alba, which is traditionally used as an anti-inflammatory, hemostatic and diuretic in Korea, yielded one novel compound, tentatively designated cornusiin H (13), together with 12 known compounds. The known compounds included four flavonoids (catechin (1), quercetin-3-O-β-D-glucuronide (2), quercetin-3-O-β-D-glucopyranoside (3), kaempferol-3-O-β-D-glucopyranoside (4)) and eight hydrolysable tannins (gallic acid (5), 2,6-di-O-galloyl-hamamelofuranoside (6), 2-galloyl-4-caffeoyl-L-threonic acid (7) 2,3-di-O-galloyl-4-caffeoyl-L-threonic acid (8), 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranoside (9), cornusiin B (10), cornusiin A (11) and camptothin B (12)). All compounds exhibited potent 1,1-diphenyl-2-picrylhydrazyl (DPPH)-free radical scavenging activity. Especially, the radical scavenging activities of 6 and 9-13 were higher than that of vitamin C. Compounds 9, 11, 12 and 13 inhibited the production of nitric oxide (NO) in lipopolysaccharide-stimulated RAW264.7 cells to the same degree as N(G)-Monomethyl-L-arginine (L-NMMA). When the antiproliferative effects of the isolated compounds were assessed in prostate cancer cells, the dimeric ellagitannins (11-13) selectively inhibited LNCaP hormone-dependent prostate cancer cells. Flow cytometry analysis indicated that the dimeric ellagitannins induced apoptosis and S-phase arrest. These results suggest that dimeric ellagitannins from Cornus alba can be developed as functional materials or herbal medicines for prostate tumors such as benign prostate hyperplasia and early-stage prostate cancer.
authors.forename: Kwan Hee
authors.initials: KH
authors.lastname: Park
authors.affiliation: Laboratory of Pharmacognosy and Natural Product based Medicine, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea. yinjun89@naver.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Laboratory of Pharmacognosy and Natural Product based Medicine, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea. ykhj33@naver.com.
authors.forename: Ki Hoon
authors.initials: KH
authors.lastname: Yoon
authors.affiliation: Laboratory of Pharmacognosy and Natural Product based Medicine, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea. g_intention@naver.com.
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Hwang
authors.affiliation: Laboratory of Pharmacognosy and Natural Product based Medicine, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea. mwlee@cau.ac.kr.
authors.forename: Min Won
authors.initials: MW
authors.lastname: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D029768:Cornus / Q000737:chemistry*; D054697:Cytostatic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects
chemical_list: D000975:Antioxidants; D054697:Cytostatic Agents; D047348:Hydrolyzable Tannins; C013515:ellagitannin; D009569:Nitric Oxide
keywords: Cornus alba; anti-inflammatory; anti-proliferation; antioxidant; ellagitannins; hydrolysable tannins; prostate cancer