A novel imidazo[1,2-a]pyridine derivative and its co-administration with curcumin exert anti-inflammatory effects by modulating the STAT3/NF-κB/iNOS/COX-2 signaling pathway in breast and ovarian cancer cell lines.

IF 2.2 4区 工程技术 Q3 PHARMACOLOGY & PHARMACY
Bioimpacts Pub Date : 2024-01-01 Epub Date: 2023-09-02 DOI:10.34172/bi.2023.27618
Havva Afshari, Shokoofe Noori, Mitra Nourbakhsh, Azam Daraei, Mahsa Azami Movahed, Afshin Zarghi
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引用次数: 0

Abstract

Introduction: Imidazo[1,2-a]pyridine derivatives with diverse pharmacological properties and curcumin, as a potential natural anti-inflammatory compound, are promising compounds for cancer treatment. This study aimed to synthesize a novel imidazo[1,2-a]pyridine derivative, (MIA), and evaluate its anti-inflammatory activity and effects on nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways, and their target genes, alone and in combination with curcumin, in MDA-MB-231 and SKOV3 cell lines.

Methods: We evaluated the interaction between imidazo[1,2-a]pyridine ligand, curcumin, and NF-κB p50 protein, using molecular docking studies. MTT assay was used to investigate the impacts of compounds on cell viability. To evaluate the NF-κB DNA binding activity and the level of inflammatory cytokines in response to the compounds, ELISA-based methods were performed. In addition, quantitative polymerase chain reaction (qPCR) and western blotting were carried out to analyze the expression of genes and investigate NF-κB and STAT3 signaling pathways.

Results: Molecular docking studies showed that MIA docked into the NF-κB p50 subunit, and curcumin augmented its binding. The MTT assay results indicated that MIA and its combination with curcumin reduced cell viability. According to the results of the ELISA-based methods, MIA lowered the levels of inflammatory cytokines and suppressed NF-κB activity. In addition, real-time PCR and Griess test results showed that the expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) genes, and nitrite production were reduced by MIA. Furthermore, the western blotting analysis demonstrated that MIA increased the expression of inhibitory κB (IκBα) and B-cell lymphoma 2 (Bcl-2)-associated X proteins (BAX), and suppressed the STAT3 phosphorylation, and Bcl-2 expression. Our findings revealed that curcumin had a potentiating role and enhanced all the anti-inflammatory effects of MIA.

Conclusion: This study indicated that the anti-inflammatory activity of MIA is exerted by suppressing the NF-κB and STAT3 signaling pathways in MDA-MB-231 and SKOV3 cancer cell lines.

一种新型咪唑[1,2- A]吡啶衍生物及其与姜黄素共给药通过调节乳腺癌和卵巢癌细胞系中STAT3/NF-κB/iNOS/COX-2信号通路发挥抗炎作用
咪唑并[1,2-a]吡啶衍生物具有多种药理性质,姜黄素作为一种潜在的天然抗炎化合物,是治疗癌症的有前途的化合物。本研究旨在合成一种新的咪唑并[1,2-a]吡啶衍生物(MIA),并在MDA-MB-231和SKOV3细胞系中评估其抗炎活性和对核因子κB(NF-κB)、信号转导子和转录激活子3(STAT3)通路及其靶基因的影响,无论是单独使用还是与姜黄素联合使用。方法:我们使用分子对接研究评估了咪唑并[1,2-a]吡啶配体、姜黄素和NF-κB p50蛋白之间的相互作用。MTT法检测化合物对细胞活力的影响。为了评估NF-κB DNA结合活性和炎症细胞因子对这些化合物的反应水平,进行了基于ELISA的方法。此外,还进行了定量聚合酶链式反应(qPCR)和蛋白质印迹来分析基因的表达,并研究NF-κB和STAT3信号通路。结果:分子对接研究表明,MIA与NF-κB p50亚基对接,姜黄素增强了其结合。MTT法检测结果表明,MIA及其与姜黄素的结合降低了细胞活力。根据基于ELISA的方法的结果,MIA降低了炎性细胞因子的水平并抑制了NF-κB的活性。此外,实时PCR和Griess测试结果显示,MIA降低了环氧合酶-2(COX-2)和诱导型一氧化氮合酶(iNOS)基因的表达和亚硝酸盐的产生。此外,western印迹分析表明,MIA增加了抑制性κB(IκBα)和B细胞淋巴瘤2(Bcl-2)相关X蛋白(BAX)的表达,并抑制STAT3磷酸化和Bcl-2表达。结论:本研究表明,姜黄素通过抑制MDA-MB-231和SKOV3癌症细胞系中的NF-κB和STAT3信号通路发挥MIA的抗炎活性。
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
Bioimpacts
Bioimpacts Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
4.80
自引率
7.70%
发文量
36
审稿时长
5 weeks
期刊介绍: BioImpacts (BI) is a peer-reviewed multidisciplinary international journal, covering original research articles, reviews, commentaries, hypotheses, methodologies, and visions/reflections dealing with all aspects of biological and biomedical researches at molecular, cellular, functional and translational dimensions.
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