Synergistic effects of epoxyazadiradione (EAD) and paclitaxel against triple-negative breast cancer cells

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2024-03-14 DOI:10.1111/fcp.13000

Kunnathully Sudhan Sijisha, Rajitha Anusha, Sulochana Priya

{"title":"Synergistic effects of epoxyazadiradione (EAD) and paclitaxel against triple-negative breast cancer cells","authors":"Kunnathully Sudhan Sijisha, Rajitha Anusha, Sulochana Priya","doi":"10.1111/fcp.13000","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Triple-negative breast cancer (TNBC) is the most aggressive and chemo-resistant form of breast cancer subtype, and chemotherapy is a vital treatment option for that. Paclitaxel is an effective chemo drug for TNBC. However, in clinical settings, paclitaxel has adverse side effects. The synergistic combination is the most promising method for overcoming undesirable toxicity and achieving a beneficial therapeutic outcome. Previous reports, including our study, showed certain anticancer potential of epoxyazadiradione (EAD), the neem limonoid, in different types of cancer cells, including TNBC.</p>\n </section>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>This study was designed to investigate the possible synergistic effects of EAD and paclitaxel against TNBC cells.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We examined the effects of EAD and paclitaxel alone and in combination in MDA-MB 231 cells, and the percentage cytotoxicity was used to calculate synergism. Characteristic apoptotic changes were observed by visualizing cellular morphology, nuclear fragmentation and membrane integrity. We further estimated anti-migratory potential of experimental compounds by wound healing assay. The reduction in inflammation during combinatorial treatment was evaluated by observing NF-κB translocation.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The combined treatment with EAD (5 μM) and paclitaxel (5 nM), which were used at doses lower than their individual IC<sub>50</sub> concentrations, showed a synergistic effect in MDA-MB-231 cells. This combination effectively induced apoptosis and antimigration and reduced the inflammatory reactions induced by the higher dose of paclitaxel.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>To conclude, EAD could be the drug of choice for combined treatment with paclitaxel in a chemotherapy regimen.</p>\n </section>\n </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fundamental & Clinical Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/fcp.13000","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Triple-negative breast cancer (TNBC) is the most aggressive and chemo-resistant form of breast cancer subtype, and chemotherapy is a vital treatment option for that. Paclitaxel is an effective chemo drug for TNBC. However, in clinical settings, paclitaxel has adverse side effects. The synergistic combination is the most promising method for overcoming undesirable toxicity and achieving a beneficial therapeutic outcome. Previous reports, including our study, showed certain anticancer potential of epoxyazadiradione (EAD), the neem limonoid, in different types of cancer cells, including TNBC.

Objective

This study was designed to investigate the possible synergistic effects of EAD and paclitaxel against TNBC cells.

Methods

We examined the effects of EAD and paclitaxel alone and in combination in MDA-MB 231 cells, and the percentage cytotoxicity was used to calculate synergism. Characteristic apoptotic changes were observed by visualizing cellular morphology, nuclear fragmentation and membrane integrity. We further estimated anti-migratory potential of experimental compounds by wound healing assay. The reduction in inflammation during combinatorial treatment was evaluated by observing NF-κB translocation.

Results

The combined treatment with EAD (5 μM) and paclitaxel (5 nM), which were used at doses lower than their individual IC₅₀ concentrations, showed a synergistic effect in MDA-MB-231 cells. This combination effectively induced apoptosis and antimigration and reduced the inflammatory reactions induced by the higher dose of paclitaxel.

Conclusion

To conclude, EAD could be the drug of choice for combined treatment with paclitaxel in a chemotherapy regimen.

查看原文本刊更多论文

环氧偶氮二酮（EAD）和紫杉醇对三阴性乳腺癌细胞的协同作用。

背景：三阴性乳腺癌（TNBC三阴性乳腺癌（TNBC）是乳腺癌亚型中最具侵袭性和化疗耐药性的一种，化疗是其重要的治疗手段。紫杉醇是治疗 TNBC 的有效化疗药物。然而，在临床应用中，紫杉醇存在不良副作用。协同联合用药是克服不良毒副作用、取得良好疗效的最有希望的方法。以往的报告（包括我们的研究）显示，楝树类柠檬素环氧氮二酮（EAD）在不同类型的癌细胞（包括 TNBC）中具有一定的抗癌潜力：本研究旨在探讨 EAD 和紫杉醇对 TNBC 细胞可能产生的协同作用：我们检测了 EAD 和紫杉醇单独或联合使用对 MDA-MB 231 细胞的作用，并使用细胞毒性百分比来计算协同作用。通过观察细胞形态、核破碎和膜完整性，我们发现了细胞凋亡的特征性变化。我们通过伤口愈合试验进一步评估了实验化合物的抗迁移潜力。通过观察 NF-κB 的转位，评估了联合治疗过程中炎症的减轻情况：结果：EAD（5 μM）和紫杉醇（5 nM）的联合治疗在 MDA-MB-231 细胞中显示出协同效应。这种组合能有效诱导细胞凋亡和抗迁移，并减少高剂量紫杉醇诱导的炎症反应：总之，EAD 可以作为化疗方案中与紫杉醇联合治疗的首选药物。

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分钟内获得全文求助全文

来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.