Caffeic Acid Phenethyl Ester Inhibits Metastatic Properties of Acid-adapted Gastric Cancer Cells.

IF 1.7 4区医学 Q4 ONCOLOGY Anticancer research Pub Date : 2025-04-01 DOI:10.21873/anticanres.17534

Sung-Chul Lim, Tae-Bum Lee, Song Iy Han

{"title":"Caffeic Acid Phenethyl Ester Inhibits Metastatic Properties of Acid-adapted Gastric Cancer Cells.","authors":"Sung-Chul Lim, Tae-Bum Lee, Song Iy Han","doi":"10.21873/anticanres.17534","DOIUrl":null,"url":null,"abstract":"Background/aim: The acidic tumor microenvironment promotes cancer invasiveness, epithelial-mesenchymal transition, and therapeutic resistance. This study aimed to investigate the long-term effects of acidic adaptation on gastric cancer cells and evaluate the anticancer properties of caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) in this context.Materials and methods: SNU601 gastric cancer cells were cultured in prolonged acidic conditions (pH 6.7) to establish an acid-adapted subline (SNU601-6.7). Invasion assays and qPCR were used to assess invasive potential and the expression of matrix metalloproteinases (MMPs). The effects of CA and CAPE on viability, apoptosis, invasion, and β-catenin expression were evaluated.Results: SNU601-6.7 cells exhibited increased invasiveness, along with upregulation of MMP2, MMP7, and MMP9. Both CA and CAPE reduced cell viability and invasion, with CAPE exerting a significantly stronger effect and inducing moderate apoptosis. Mechanistic studies revealed that CAPE decreased total and nuclear β-catenin levels, and inhibited AKT and GSK3β phosphorylation. Further, pharmacological inhibition of AKT pathway confirmed its role in β-catenin accumulation and cell invasiveness.Conclusion: These findings identify CAPE as a potent inhibitor of invasion in acid-adapted gastric cancer cells by targeting the AKT/β-catenin pathway, highlighting its potential as a therapeutic candidate for gastric cancer in acidic tumor microenvironments.","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 4","pages":"1525-1534"},"PeriodicalIF":1.7000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anticancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/anticanres.17534","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background/aim: The acidic tumor microenvironment promotes cancer invasiveness, epithelial-mesenchymal transition, and therapeutic resistance. This study aimed to investigate the long-term effects of acidic adaptation on gastric cancer cells and evaluate the anticancer properties of caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) in this context.

Materials and methods: SNU601 gastric cancer cells were cultured in prolonged acidic conditions (pH 6.7) to establish an acid-adapted subline (SNU601-6.7). Invasion assays and qPCR were used to assess invasive potential and the expression of matrix metalloproteinases (MMPs). The effects of CA and CAPE on viability, apoptosis, invasion, and β-catenin expression were evaluated.

Results: SNU601-6.7 cells exhibited increased invasiveness, along with upregulation of MMP2, MMP7, and MMP9. Both CA and CAPE reduced cell viability and invasion, with CAPE exerting a significantly stronger effect and inducing moderate apoptosis. Mechanistic studies revealed that CAPE decreased total and nuclear β-catenin levels, and inhibited AKT and GSK3β phosphorylation. Further, pharmacological inhibition of AKT pathway confirmed its role in β-catenin accumulation and cell invasiveness.

Conclusion: These findings identify CAPE as a potent inhibitor of invasion in acid-adapted gastric cancer cells by targeting the AKT/β-catenin pathway, highlighting its potential as a therapeutic candidate for gastric cancer in acidic tumor microenvironments.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

咖啡酸苯乙酯可抑制酸性胃癌细胞的转移特性

背景/目的：酸性肿瘤微环境促进肿瘤侵袭、上皮-间质转化和治疗耐药。本研究旨在探讨酸性适应对胃癌细胞的长期影响，并在此背景下评价咖啡酸（CA）和咖啡酸苯乙酯（CAPE）的抗癌特性。材料与方法：将SNU601胃癌细胞在长时间酸性条件下（pH 6.7）培养，建立适应酸性亚系（SNU601-6.7）。采用侵袭性实验和qPCR技术评估基质金属蛋白酶（MMPs）的侵袭潜能和表达。观察CA和CAPE对细胞活力、凋亡、侵袭及β-catenin表达的影响。结果：SNU601-6.7细胞侵袭性增强，MMP2、MMP7和MMP9表达上调。CA和CAPE均可降低细胞活力和侵袭，其中CAPE的作用更强，可诱导适度凋亡。机制研究表明，CAPE降低总β-catenin和核β-catenin水平，抑制AKT和GSK3β磷酸化。此外，药理抑制AKT通路证实了其在β-catenin积累和细胞侵袭中的作用。结论：这些研究结果表明，CAPE通过靶向AKT/β-catenin通路，可有效抑制胃酸适应性胃癌细胞的侵袭，突出了其作为酸性肿瘤微环境下胃癌治疗候选药物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.