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: Kwan Hee Park, Jun Yin, Ki Hoon Yoon, Yoon Jeong Hwang, Min Won Lee
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 21 Issue 2 Pg. 137 (Jan 23 2016) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 26805810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Cytostatic Agents
• Hydrolyzable Tannins
• ellagitannin
• Nitric Oxide

Topics

• Animals
• Antioxidants (chemistry, pharmacology)
• Apoptosis
• Cell Line, Tumor
• Cornus (chemistry)
• Cytostatic Agents (chemistry, isolation & purification, pharmacology)
• Humans
• Hydrolyzable Tannins (chemistry, isolation & purification, pharmacology)
• Macrophages (cytology, drug effects)
• Male
• Mice
• Molecular Structure
• Nitric Oxide (metabolism)
• Prostatic Neoplasms (drug therapy, metabolism)
• RAW 264.7 Cells
• S Phase Cell Cycle Checkpoints (drug effects)