The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathway
The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathway
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DOI：
10.1016/j.jnutbio.2005.09.004
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发表时间：
2006-09-01
影响因子：
5.6
通讯作者：
Espin, Juan Carlos
中科院分区：
文献类型：
--
作者：
Larrosa, Mar;Tomas-Barberan, Francisco A.;Espin, Juan Carlos
富含多酚的饮食食品因其具有抗癌、化学预防和化学治疗的特性而受到人们的关注。鞣皮单宁(Ets)是一种存在于草莓、覆盆子、核桃、石榴、橡木陈酿红酒等植物中的所谓可水解性单宁。据报道，Ets及其水解物--鞣花酸(Ea)均可诱导肿瘤细胞的凋亡。海藻单宁不会在体内被吸收，但会到达结肠，释放由人体微生物群代谢的EA。我们的目的是研究饮食中的ET和EA对人结肠癌Caco-2细胞和结肠正常Ccd-112CoN细胞的影响。PUPI和EA对Caco-2细胞的作用相同：细胞周期蛋白A和B下调，细胞周期蛋白E上调，细胞周期停滞于S期，通过bclxl下调内源性途径(Fas非依赖性，caspase8非依赖性)诱导细胞凋亡，线粒体释放细胞色素c进入胞浆，激活启动子caspase9和效应子caspase3。电针和电针均未诱导正常结肠癌细胞的凋亡(未检测到染色质凝聚和caspase3和9的激活)。在Caco-2细胞的情况下，Ppui没有特殊的作用，因为它在介质中被水解产生EA，EA进入细胞并被代谢产生二甲基EA的衍生物。我们的研究表明，膳食ETS的抗癌作用可能主要是由于其水解物EA通过线粒体途径诱导结肠癌Caco-2细胞凋亡，而不是通过正常结肠细胞。(C)2006 Elsevier Inc.保留所有权利。
Polyphenol-rich dietary foodstuffs have attracted attention due to their cancer chemopreventive and chemotherapeutic properties. Ellagitannins (ETs) belong to the so-called hydrolysable tannins found in strawberries, raspberries, walnuts, pomegranate, oak-aged red wine, etc. Both ETs and their hydrolysis product, ellagic acid (EA), have been reported to induce apoptosis in tumour cells. Ellagitannins are not absorbed in vivo but reach the colon and release EA that is metabolised by the human microflora. Our aim was to investigate the effect of a dietary ET [pomegranate punicalagin (PUNI)] and EA on human colon cancer Caco-2 and colon normal CCD-112CoN cells. Both PUNI and EA provoked the same effects on Caco-2 cells: down-regulation of cyclins A and B I and upregulation of cyclin E, cell-cycle arrest in S phase, induction of apoptosis via intrinsic pathway (FAS-independent, caspase 8-independent) through bcl-XL down-regulation with mitochondrial release of cytochrome c into the cytosol, activation of initiator caspase 9 and effector caspase 3. Neither EA nor PUNI induced apoptosis in normal colon CCD-112CoN cells (no chromatin condensation and no activation of caspases 3 and 9 were detected). In the case of Caco-2 cells, no specific effect can be attributed to PUNI since it was hydrolysed in the medium to yield EA, which entered into the cells and was metabolised to produce dimethyl-EA derivatives. Our study suggests that the anticarcirrogenic effect of dietary ETs could be mainly due to their hydrolysis product, EA, which induced apoptosis via mitochondrial pathway in colon cancer Caco-2 cells but not in normal colon cells. (c) 2006 Elsevier Inc. All rights reserved.