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Extracts from stems, leaves, and fruits show hemolytic activity and modest antioxidant capacity, while exhibiting dose-dependent cytotoxicity that is strongest for fruit extracts. The cytotoxic effect is linked to apoptosis induction, with fruit extracts lowering the BCL-2/BAX ratio. Combined treatment with cisplatin increases cytotoxicity and cell aggregation compared with either agent alone. GC-MS and polyphenol/flavonoid analyses suggest the presence of compounds with anti-cancer potential.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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Medicago orbicularis Antioxidant, Antihemolytic, and Anti-Cancerous Activities and Its Augmentation of Cisplatin-Induced Cytotoxicity in A549 Lung Cancer Cells  \nAbdullah A. Shaito 1,2, *, Islam Omairi 3,4, Najlaa Al-Thani 5, Fatiha Seglab 1, Esraa Ad-Darwish 6, Firas Kobeissy 7, * and Salam Nasreddine 4,8, *  \nCitation: Shaito, A.A.; Omairi, I.; Al-Thani, N.; Seglab, F.; Ad-Darwish, E.; Kobeissy, F.; Nasreddine, S. Determination of Medicago orbicularis Antioxidant, Antihemolytic, and Anti-Cancerous Activities and Its Augmentation of Cisplatin-Induced Cytotoxicity in A549 Lung Cancer Cells. Plants 2024, 13, 442. [https://](https://)[ ](https://)[doi.org/10.3390/plants13030442](doi.org/10.3390/plants13030442)  \nAcademic Editors: Rodica-Mihaela Dinic and Bianca Furdui  \nReceived: 16 September 2023  \nRevised: 25 October 2023  \nAccepted: 27 October 2023  \nPublished: 2 February 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar  \n2 College of Medicine and Department of Biomedical Sciences at College of Health Sciences, Qatar University, Doha P.O. Box 2713, Qatar  \n3 Department of Biological and Chemical Sciences, Faculty of Arts and Sciences, Lebanese International University, Beirut 1105, Lebanon  \n4 Biology Department, Faculty of Sciences-Section I, Group of Anti-Cancer Therapeutic Approaches (ATAC), Laboratory Rammal Rammal, Lebanese University, Beirut 1102, Lebanon  \n5 Research and Development Department, Barzan Holdings, Doha P.O. Box 7178, Qatar  \n6 Biotechnology in Forensic Science Program, Faculty of Health Sciences, American University of Science and Technology, Beirut 1100, Lebanon  \n7 Department of Neurobiology, Center for Neurotrauma, Multiomics & Biomarkers (CNMB), More-House School of Medicine, 720 Westview Dr. SW, Atlanta, GA 30310, USA  \n8 Doctoral School of Science and Technology, Research Platform for Environmental Science (PRASE), Lebanese University, Beirut 1102, Lebanon  \n* Correspondence: abdshaito@qu.edu.qa (A.A.S.); firasko@gmail.com (F.K.); salam.nasreddine@ul.edu.lb (S.N.) Abstract: The anti-lung cancer properties of the plant Medicago orbicularis have not been explored yet. Therefore, we identified its phytochemical composition and investigated the antioxidant, antihemolytic, and anti-cancerous properties of extracts of this plant in A549 human lung adenocarcinoma cells. The results show that all parts of M. orbicularis (stems, leaves, and fruits) exhibit remarkable hemolytic activities and modest antioxidant capacity. In addition, all extracts showed a dose-dependent anti-cancerous cytotoxic activity against A549 cells, with fruit extracts being the most potent. This cytotoxic effect could be related, at least partly, to the induction of apoptosis, where M. orbicularis fruit extracts reduced the ratio of anti-apoptotic BCL-2/pro-apoptotic BAX, thereby promoting cellular death. Furthermore, the use of M. orbicularis, in combination with a conventional chemotherapeutic agent, cisplatin, was assessed. Indeed, the combination of cisplatin and M. orbicularis fruit extracts was more cytotoxic and induced more aggregation of A549 cells than either treatment alone. GC-MS analysis and total polyphenol and flavonoid content determination indicated that M. orbicularis is rich in compounds that have anti-cancerous effects. We propose M. orbicularis as a potential source of anti-cancerous agents to manage the progression of lung cancer and its resistance to therapy.  \nKeywords: Medicago orbicularis; lung cancer; herbal medicine; antioxidants; hemolytic; cisplatin; A549 cells  \n1. Introduction  \nCan","cbCaidU4KITVWNGZ","https://ap.wps.com/l/cbCaidU4KITVWNGZ","pdf",9506058,"English","# Introduction\n## Cancer burden and lung cancer challenges\n# Materials and Methods\n## Extraction and phytochemical analysis\n## Antioxidant and antihemolytic assessments\n## Anti-cancer activity and combination with cisplatin\n# Results\n## Cytotoxic effects in A549 cells\n## Apoptosis-related biomarker changes\n## Enhancement of cisplatin-induced effects\n# Discussion\n## Mechanistic interpretation and therapeutic implications","[{\"question\":\"What components of Medicago orbicularis were evaluated in A549 lung cancer cells?\",\"answer\":\"Stems, leaves, and fruits were investigated using plant extracts to assess antioxidant, antihemolytic, and anti-cancerous properties.\"},{\"question\":\"How did Medicago orbicularis extracts affect cell death and apoptosis markers?\",\"answer\":\"Fruit extracts displayed the strongest dose-dependent cytotoxic activity, associated at least partly with apoptosis induction and a reduced anti-apoptotic BCL-2/pro-apoptotic BAX ratio.\"},{\"question\":\"What was the effect of combining Medicago orbicularis with cisplatin?\",\"answer\":\"Cisplatin combined with Medicago orbicularis fruit extracts produced greater cytotoxicity and increased aggregation of A549 cells than either treatment alone.\"}]","Determination of Medicago orbicularis Antioxidant, Antihemolytic, and Anti-Cancerous Activities - Its Augmentation of Cisplatin-Induced Cytotoxicity in A549 Lung Cancer Cells | PDF",1789987168]