Department of Food and Nutrition, and Research Institute of Human Ecology, Seoul National University, Seoul, 151-742, Korea.
Food Funct. 2015 May;6(5):1675-83. 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.
黑莓（BRB）种子是水果加工后的主要废弃物。种子富含鞣花单宁（ET），这是一类可水解单宁，可水解为鞣花酸（EA），进一步代谢为尿石素 A（UA）和尿石素 B（UB），已知在结肠和前列腺中具有生物利用度。在这项研究中，评估了这些化合物对 HT-29 结肠癌细胞的抗癌活性。ET、EA、UA 和 UB 抑制癌细胞的增殖。EA 导致细胞周期轻微但显著地停滞在 G1 期，而尿石素导致细胞周期停滞在 G2/M 期并上调 p21 表达。用化合物处理时，通过 Annexin V-FITC/PI 测定检测到凋亡细胞。线粒体膜电位的破坏和半胱天冬酶 8 和 9 的激活表明可能涉及外在和内在的凋亡途径。半胱天冬酶 3 的激活和 PARP 的裂解进一步证实了凋亡的诱导。ET、EA、UA 和 UB 通过在 HT-29 人结肠癌细胞上阻滞细胞周期和诱导细胞凋亡来发挥抗癌作用。本研究表明，BRB 种子可能是抗癌 ET 的潜在来源。
