In vitro antioxidant and antiproliferative effects of ellagic acid and its colonic metabolite, urolithins, on human bladder cancer T24 cells
In vitro antioxidant and antiproliferative effects of ellagic acid and its colonic metabolite, urolithins, on human bladder cancer T24 cells
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DOI：
10.1016/j.fct.2013.06.025
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发表时间：
2013-09-01
影响因子：
4.3
通讯作者：
Zhu, Fan
中科院分区：
文献类型：
--
作者：
Qiu, Zhenpeng;Zhou, Benhong;Zhu, Fan
尿石素是鞣花酸在胃肠道内被肠道菌群代谢的产物。在以往的研究中发现尿石素主要抑制前列腺癌和结肠癌细胞的生长。然而，尿石素治疗膀胱癌尚无报道。本文研究了3种尿石素类化合物（尿石素A、尿石素B、8- ome -尿石素A）和鞣花酸对人膀胱癌细胞株T24的体外抗增殖活性。尿素A、尿素B、8- ome -尿素A和鞣花酸对T24细胞抑制的IC50值分别为43.9、35.2、46.3和33.7 μ M。在给药后，我们发现这些化合物可以增加T24细胞中Phospho-p38 MAPK的mRNA和蛋白表达，降低MEKK1和Phospho-c-Jun的mRNA和蛋白表达。在药物诱导的细胞凋亡中，Caspase-3也被激活，ppar - γ蛋白表达增加。此外，三种尿石素和EA处理的抗氧化实验表明，h2o2处理的T24细胞胞内ROS和MDA水平降低，SOD活性升高。结果表明，这些化合物可以通过p38-MAPK和/或c-Jun药物caspase-3激活抑制膀胱癌细胞增殖，降低氧化应激状态。(C) 2013 Elsevier Ltd.版权所有。
Urolithins were the metabolites of ellagic acid by intestinal flora in gastrointestinal tract. In previous research, it was found that urolithins could mainly inhibit prostate cancer and colon cancer cell growth. However, there is no report about bladder cancer therapy of urolithins. In this paper, three urolithin-type compounds (urolithin A, urolithin B, 8-OMe-urolithin A) and ellagic acid were evaluated for antiproliferative activity in vitro against human bladder cancer cell lines T24. The IC50 values for T24 cell inhibition were 43.9, 35.2, 46.3 and 33.7 mu M for urolithin A, urolithin B, 8-OMe-urolithin A and ellagic acid, respectively. After the administration of urolithins and ellagic acid, we found these compounds could increase mRNA and protein expression of Phospho-p38 MAPK, and decrease mRNA and protein expression of MEKK1 and Phospho-c-Jun in T24 cells. Caspase-3 was also activated and PPAR-gamma protein expression increased in drug-induced apoptosis. And what's more, the antioxidant assay afforded by three urolithins and EA treatments were associated with decreases in the intracellular ROS and MDA levels, and increased SOD activity in H2O2-treated T24 cells. The results suggested that these compounds could inhibit cell proliferation by p38-MAPK and/or c-Jun medicated caspase-3 activation and reduce the oxidative stress status in bladder cancer. (C) 2013 Elsevier Ltd. All rights reserved.