Elsayed I. Salim, Safaa Elsebakhy, Mohamed Hessien
{"title":"Repurposing of atorvastatin and metformin denotes their individual and combined antiproliferative effects in non-small cell lung cancer","authors":"Elsayed I. Salim, Safaa Elsebakhy, Mohamed Hessien","doi":"10.1111/fcp.12981","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Due to the limited success in the treatment of lung adenocarcinomas, new treatment protocols are urgently needed to increase the curability rate and the survival of lung cancer patients.</p>\n </section>\n \n <section>\n \n <h3> Objectives</h3>\n \n <p>Although statins, like atorvastatin (Ator), and metformin (Met) are widely accepted as hypolipidemic and hypoglycemic drugs, respectively, there are many predictions about their enhancing antitumor effect when they are combined with traditional chemotherapeutics.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The individual and combined antiproliferative potential of Ator and Met was tested by MTT-assay in non-small cell lung cancer (NSCLC) A549 cell line, compared to the corresponding effect of Gemcitabine (Gem) with implication on the mechanisms of action.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Initially, both drugs demonstrated concentration-dependent cytotoxicity in A549 cells. Also, their combination index (CI) indicated their synergistic effect at equi-IC50 concentration (CI = 0.00984). Moreover, Ator and/or Met-treated cells revealed disrupted patterns of SOD, CAT, GSH, MDA, and TAC, developed apoptosis, and larger fractions of the cell population were arrested in G0/G1 phase, particularly in cells dually-treated both Ator and Met. These observations were accompanied by downregulation in the expression of <i>iNOS</i>, <i>HO-1</i>, and the angiogenic marker <i>VEGF</i>, meanwhile, an altered expression of <i>MAPK</i> and <i>AMPK</i> was observed.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Conclusively, these data suggest that repurposing of Ator and Met demonstrates their individual and combined antiproliferative effect in non-small cell lung cancer and they may adopt a similar mechanism of action.</p>\n </section>\n </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-01-23","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.12981","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
Due to the limited success in the treatment of lung adenocarcinomas, new treatment protocols are urgently needed to increase the curability rate and the survival of lung cancer patients.
Objectives
Although statins, like atorvastatin (Ator), and metformin (Met) are widely accepted as hypolipidemic and hypoglycemic drugs, respectively, there are many predictions about their enhancing antitumor effect when they are combined with traditional chemotherapeutics.
Methods
The individual and combined antiproliferative potential of Ator and Met was tested by MTT-assay in non-small cell lung cancer (NSCLC) A549 cell line, compared to the corresponding effect of Gemcitabine (Gem) with implication on the mechanisms of action.
Results
Initially, both drugs demonstrated concentration-dependent cytotoxicity in A549 cells. Also, their combination index (CI) indicated their synergistic effect at equi-IC50 concentration (CI = 0.00984). Moreover, Ator and/or Met-treated cells revealed disrupted patterns of SOD, CAT, GSH, MDA, and TAC, developed apoptosis, and larger fractions of the cell population were arrested in G0/G1 phase, particularly in cells dually-treated both Ator and Met. These observations were accompanied by downregulation in the expression of iNOS, HO-1, and the angiogenic marker VEGF, meanwhile, an altered expression of MAPK and AMPK was observed.
Conclusion
Conclusively, these data suggest that repurposing of Ator and Met demonstrates their individual and combined antiproliferative effect in non-small cell lung cancer and they may adopt a similar mechanism of action.
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.