title: Chemopreventive activity of ellagitannins and their derivatives from black raspberry seeds on HT-29 colon cancer cells.
abstract: Black raspberry (BRB) seeds are a major waste product after fruit processing. The seeds are abundant in ellagitannins (ET), a class of hydrolysable tannins, which are hydrolyzed to ellagic acid (EA) and further metabolized to urolithin A (UA) and urolithin B (UB), known to be bioavailable in the colon and the prostate. In this study, the anti-cancer activities of these compounds were evaluated on HT-29 colon cancer cells. ET, EA, UA and UB inhibited the proliferation of the cancer cells. EA caused a slight, but significant cell cycle arrest at the G1 phase, and urolithins caused cell cycle arrest at the G2/M phase and upregulated p21 expression. Apoptotic cells were detected by Annexin V-FITC/PI assay when treated with the compounds. Disruption in mitochondrial membrane potential and activation of caspases 8 and 9 suggest that both extrinsic and intrinsic apoptotic pathways may be involved. Activation of caspase 3 and cleavage of PARP further confirmed the induction of the apoptosis. ET, EA, UA and UB showed anti-cancer activity by arresting the cell cycle and inducing apoptosis on HT-29 human colon cancer cells. This study suggests that the BRB seeds could be a potential source of anti-cancer ET.
authors.affiliation: Department of Food and Nutrition, and Research Institute of Human Ecology, Seoul National University, Seoul, 151-742, Korea. keum@snu.ac.kr.
authors.forename: Hyunnho
authors.initials: H
authors.lastname: Cho
authors.forename: Hana
authors.initials: H
authors.lastname: Jung
authors.forename: Heejae
authors.initials: H
authors.lastname: Lee
authors.forename: Hae Chang
authors.initials: HC
authors.lastname: Yi
authors.forename: Ho-kyung
authors.initials: HK
authors.lastname: Kwak
authors.forename: Keum Taek
authors.initials: KT
authors.lastname: Hwang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D065856:Rubus / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; C013515:ellagitannin; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053181:Caspase 8