Chlorogenic Acid Inhibits Proliferation, Migration and Invasion of Pancreatic Cancer Cells via AKT/GSK-3β/β-catenin Signaling Pathway.

IF 2.5 4区 医学 Q3 ONCOLOGY Recent patents on anti-cancer drug discovery Pub Date : 2024-01-01 DOI:10.2174/1574892818666230327134746
Xiaoliang Chen, Binyu Liu, Jiale Tong, Jianing Bo, Miao Feng, Lili Yin, Xiukun Lin
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Abstract

Background: Chlorogenic acid (CA, United States Patent No. 10772340), a natural biologically active food ingredient, displays potent antitumor activity against a variety of cancer cells. However, the mechanism underlying its anticancer effect is not well elucidated.

Objective: In the present study, we hope to dissect the mechanism underlying the anticancer effects of CA in pancreatic cancer cells.

Methods: The cytotoxicity of CA in pancreatic cancer cells was determined by MTT assay. Flow cytometry was performed to evaluate the cells apoptosis, while a clonogenic assay was carried out to check the colony formation of cancer cells. Transwell assay was performed to assess the cells migration and invasion. The protein expression of AKT/GSK-3β/β-catenin signaling pathway was detected by Western Blot.

Results: Our data indicated that CA inhibited the proliferation of PANC-28 and PANC-1 cells in a dose and time-dependent manner. CA was able to inhibit colony formation, migration, and invasion ability and trigger apoptosis in PANC-28 and PANC-1 cells. Further study showed that CA down-regulated the expression of AKT, p-AKT(Thr308), p-GSK-3β(Ser9), β-catenin, N-cadherin, and vimentin while enhancing the expression of cleaved-caspase 3 and cleaved-caspase 7 in PANC-28 and PANC-1 cells.

Conclusion: Our study provides significant evidence that CA is able to inhibit the growth of pancreatic cancer via the AKT/GSK-3β/β-catenin signaling pathway.

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绿原酸通过AKT/GSK-3β/β-catenin信号通路抑制胰腺癌症细胞增殖、迁移和侵袭。
绿原酸(CA,美国专利号10772340)是一种天然生物活性食品成分,对多种癌症细胞显示出强大的抗肿瘤活性。然而,其抗癌作用的机制尚不清楚。在本研究中,我们希望剖析CA在胰腺癌症细胞中抗癌作用的机制。用MTT法测定CA对癌症细胞的细胞毒性。流式细胞仪检测细胞凋亡,克隆形成检测癌症细胞集落形成。进行Transwell测定以评估细胞迁移和侵袭。Western Blotting法检测了AKT/GSK-3β/β-catenin信号通路的蛋白表达。我们的数据表明,CA以剂量和时间依赖的方式抑制PANC-28和PANC-1细胞的增殖。CA能够抑制PANC-28和PANC-1细胞的集落形成、迁移和侵袭能力,并引发细胞凋亡。进一步的研究表明,CA下调了PANC-28和PANC-1细胞中AKT、p-AKT(Thr308)、p-GSK-3β(Ser9)、β-连环蛋白、N-钙粘蛋白和波形蛋白的表达,同时增强了切割的胱天蛋白酶7的表达。我们的研究提供了重要的证据,表明CA能够通过AKT/GSK-3β/β-catenin信号通路抑制癌症的生长。
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来源期刊
CiteScore
4.50
自引率
7.10%
发文量
55
审稿时长
3 months
期刊介绍: Aims & Scope Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.
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