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胡椒碱通过 ROS-线粒体相关信号通路影响胃癌细胞凋亡和增殖的机制。

Mechanism of piperine in affecting apoptosis and proliferation of gastric cancer cells via ROS-mitochondria-associated signalling pathway.

机构信息

Department of Center Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.

Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.

出版信息

J Cell Mol Med. 2021 Oct;25(20):9513-9522. doi: 10.1111/jcmm.16891. Epub 2021 Aug 31.

Abstract

Piperine (PIP), the main active ingredient in pepper, belongs to the cinnamamide alkaloid. PIP has been found to have functions, including anti-oxidation, immune regulation, anti-tumour and promotion of drug metabolism. The present study was mainly designed to reveal the anti-tumour effect of PIP against gastric cancer and the relevant mechanism. In brief, the undifferentiated human gastric cancer cell HGC-27 was used, which was treated with different concentrations of PIP. As a result, PIP could inhibit proliferation and induce apoptosis of HGC-27 cells in a dose-dependent manner. The mechanism of PIP was associated with ROS increase and mitochondrial damage, simultaneously, the expression of key proteins of apoptosis was affected, including Bcl-2, Bax, Cyt-c, Caspase-9 and Caspase-3. Pre-treatment of ROS scavenger NAC HGC-27 cells could significantly reduce PIP-induced apoptosis and inhibit the activation of apoptotic signals. Consistently, PIP could induce ROS to increase and activate apoptotic signals in the animal model. Therefore, the present study showed that PIP can induce the generation of ROS, thereby promoting the activation of mitochondrial apoptotic pathway and exerting anti-tumour effects.

摘要

胡椒碱(PIP)是辣椒中的主要活性成分,属于肉桂酰胺生物碱。已经发现 PIP 具有多种功能,包括抗氧化、免疫调节、抗肿瘤和促进药物代谢。本研究主要旨在揭示 PIP 对胃癌的抗肿瘤作用及其相关机制。简要而言,使用未分化的人胃癌细胞 HGC-27,用不同浓度的 PIP 处理。结果表明,PIP 能够以剂量依赖的方式抑制 HGC-27 细胞的增殖并诱导其凋亡。PIP 的作用机制与 ROS 增加和线粒体损伤有关,同时影响凋亡关键蛋白的表达,包括 Bcl-2、Bax、Cyt-c、Caspase-9 和 Caspase-3。用 ROS 清除剂 NAC 预处理 HGC-27 细胞可以显著减少 PIP 诱导的细胞凋亡,并抑制凋亡信号的激活。同样,PIP 可以在动物模型中诱导 ROS 增加并激活凋亡信号。因此,本研究表明 PIP 可以诱导 ROS 的产生,从而促进线粒体凋亡途径的激活,发挥抗肿瘤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8176/8505830/a21e17911a02/JCMM-25-9513-g001.jpg

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