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可可茶(厚皮香)通过 ROS 生成和 PI3K/Akt 信号通路诱导 HCT116 细胞线粒体依赖性凋亡。

Cocoa tea (Camellia ptilophylla) induces mitochondria-dependent apoptosis in HCT116 cells via ROS generation and PI3K/Akt signaling pathway.

机构信息

State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; College of Food Science, South China Agricultural University, Tianhe District, 483 Wushan Street, Guangzhou 510642, China.

College of Food Science, South China Agricultural University, Tianhe District, 483 Wushan Street, Guangzhou 510642, China.

出版信息

Food Res Int. 2020 Mar;129:108854. doi: 10.1016/j.foodres.2019.108854. Epub 2019 Dec 2.

DOI:10.1016/j.foodres.2019.108854
PMID:32036895
Abstract

Cocoa tea (Camellia ptilophylla), a natural gallocatechin gallate (GCG)-rich and low caffeine-containing tea species, has been recently reported to possess various bioactivities. However, the anti-colon cancer effects of Cocoa tea and its underlying mechanisms remain virtually unknown. This study aimed to assess the anti-proliferative and pro-apoptotic effects of water extract of Cocoa tea (CWE) on human colon cancer HCT116 cells compared with Yunnan Daye tea (YWE). Primarily, CWE showed stronger anti-proliferation and apoptosis induction than YWE. Moreover, reduction of mitochondrial membrane potential (MMP), up-regulation of Bax/Bcl-2 ratio, release of cytochrome c, activation of caspase-9 and -3, and cleavage of poly (ADP-ribose) polymerase (PARP) were observed, suggesting that mitochondrial apoptotic pathway was activated by CWE. Furthermore, CWE-induced apoptosis in HCT116 cells was dependent on the generation of intracellular reactive oxygen species (ROS) and down-regulation of phosphatidylinositol-3-kinase (PI3K)/Akt pathway. Pretreatment with ROS scavenger N-acetyl cysteine (NAC) attenuated the impact of CWE on mitochondria-related apoptosis proteins, and partially recovered the inhibition of Akt phosphorylation. These results indicated that ROS generation mediated mitochondrial dysfunction and inactivation of PI3K/Akt pathway in CWE-induced HCT116 cell apoptosis. Additionally, CWE significantly inhibited tumor growth in HCT116 tumor-bearing mice, suggesting that Cocoa tea could act as a potential functional beverage to prevent or treat colorectal cancer.

摘要

可可茶(Camellia ptilophylla)是一种天然富含没食子儿茶素没食子酸酯(GCG)且咖啡因含量低的茶类,最近有报道称其具有多种生物活性。然而,可可茶抗结肠癌的作用及其潜在机制尚不清楚。本研究旨在评估可可茶水提物(CWE)与云南大叶茶(YWE)相比对人结肠癌细胞 HCT116 的抗增殖和促凋亡作用。首先,CWE 显示出比 YWE 更强的抗增殖和诱导凋亡作用。此外,还观察到线粒体膜电位(MMP)降低、Bax/Bcl-2 比值升高、细胞色素 c 释放、caspase-9 和 -3 激活以及多聚(ADP-核糖)聚合酶(PARP)裂解,表明 CWE 通过线粒体凋亡途径激活。此外,CWE 诱导 HCT116 细胞凋亡依赖于细胞内活性氧(ROS)的产生和磷脂酰肌醇-3-激酶(PI3K)/Akt 通路的下调。用 ROS 清除剂 N-乙酰半胱氨酸(NAC)预处理可减弱 CWE 对线粒体相关凋亡蛋白的影响,并部分恢复 Akt 磷酸化的抑制。这些结果表明,ROS 生成介导了 CWE 诱导的 HCT116 细胞凋亡中线粒体功能障碍和 PI3K/Akt 通路失活。此外,CWE 显著抑制 HCT116 荷瘤小鼠的肿瘤生长,表明可可茶可能作为一种潜在的功能性饮料,用于预防或治疗结直肠癌。

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