Chemopreventive activity of ellagitannins and their derivatives from black raspberry seeds on HT-29 colon cancer cells

• Published in: Food & function 2015-05, Vol.6 (5), p.1675-1683
• Main Authors: Cho, Hyunnho, Jung, Hana, Lee, Heejae, Yi, Hae Chang, Kwak, Ho-kyung, Hwang, Keum Taek
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase 8 - genetics; Caspase 8 - metabolism; Cell Cycle - drug effects; Cell Proliferation - drug effects; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - physiopathology; Colonic Neoplasms - prevention & control; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; HT29 Cells; Humans; Hydrolyzable Tannins - pharmacology; Plant Extracts - pharmacology; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - metabolism; Rubus - chemistry; Seeds - chemistry
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/c5fo00274e

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. Cell cycle arrest and apoptosis were induced by black raspberry seed ellagitannins and their metabolites, ellagic acid and urolithins.