Parthenolide induces ROS-dependent cell death in human gastric cancer cell.

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Clinical and Experimental Medicine Pub Date : 2024-11-01 DOI:10.17219/acem/175152

Dandan Han, Wenhao Zhu, Yang Chen, Huiru Wang

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引用次数: 0

Abstract

Background: Parthenolide (PN), a key active ingredient of feverfew, has been used to treat gastrointestinal disorders. However, the mechanism of the cytotoxic effect exerted by PN on tumor cells has not been elucidated.

Objectives: To study the cytotoxic effect of PN on human gastric cancer cells, the specific death mode, and gene expression changes induced by PN.

Material and methods: In this study, MGC-803 cells were used to study PN-induced cytotoxicity as a gastric cancer cell line. Assays of cell proliferation, cell cycle distribution, apoptosis, and reactive oxygen species (ROS) were performed using a Cell Counting Kit-8 (CCK-8) assay and a flow cytometer. MGC-803 cells treated with and without PN were separately subjected to high-throughput RNA sequencing. Western blotting was used to investigate the expression of some important proteins.

Results: Parthenolide exposure elicited cell proliferation inhibition in a doseand time-dependent manner. Parthenolide induced cell cycle arrest at the G1 and S stages. Parthenolide-induced caspase-dependent apoptosis and necroptosis were caused by the activation of RIP, RIP3 and MLKL. MGC-803 cells showed a response to ROS and oxidative stress after PN treatment. Moreover, ROS and cytotoxicity induced by PN were significantly attenuated by a ROS scavenger catalase.

Conclusions: Parthenolide-induced gastric cancer cell death is a complex ROS-dependent process different from ordinary apoptosis and necrosis, suggesting that PN is a potential treatment option for gastric cancer.

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帕氏内酯诱导人胃癌细胞发生 ROS 依赖性细胞死亡

背景：马钱子内酯（Parthenolide，PN）是马钱子的一种主要活性成分，已被用于治疗胃肠道疾病。然而，PN 对肿瘤细胞产生细胞毒性作用的机制尚未阐明：研究 PN 对人胃癌细胞的细胞毒性作用、特异性死亡模式以及 PN 诱导的基因表达变化：本研究以 MGC-803 细胞作为胃癌细胞系，研究 PN 诱导的细胞毒性。使用细胞计数试剂盒-8（CCK-8）和流式细胞仪对细胞增殖、细胞周期分布、细胞凋亡和活性氧（ROS）进行检测。使用和不使用 PN 处理的 MGC-803 细胞分别进行了高通量 RNA 测序。用 Western 印迹法检测了一些重要蛋白质的表达：结果：帕氏内酯暴露以剂量和时间依赖性方式抑制细胞增殖。帕氏内酯诱导细胞周期停滞在 G1 和 S 阶段。Parthenolide诱导的树突酶依赖性凋亡和坏死是由RIP、RIP3和MLKL激活引起的。经 PN 处理后，MGC-803 细胞出现了对 ROS 和氧化应激的反应。此外，ROS清除剂过氧化氢酶能显著减轻PN诱导的ROS和细胞毒性：结论：帕氏内酯诱导的胃癌细胞死亡是一个复杂的 ROS 依赖性过程，不同于普通的细胞凋亡和坏死，这表明帕氏内酯是一种潜在的胃癌治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Clinical and Experimental Medicine MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.70

自引率

4.80%

发文量

153

审稿时长

6-12 weeks

期刊介绍： Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly. Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff. Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj. Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker. The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition. In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus. Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.