{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:16:25Z","timestamp":1785129385840,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNPq"},{"name":"Faperj"},{"name":"Proppi-UFF"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Objectives: This study analyzed the antiproliferative potential of Eugenia uniflora L. leaf extracts against cervical cancer and non-cancerous cell lines. Methods: The extracts were prepared by maceration using hexane (EUH), dichloromethane (EUD), and ethyl acetate (EUA). Their cytotoxic potential was evaluated through MTT assays, wound healing assays, and flow cytometry. To identify classes of secondary metabolites, total phenolic and flavonoid contents were quantified using spectrophotometric methods, and individual metabolites were tentatively identified by LC-MS\/MS. Results: EUH, EUD. and EUA exhibited cytotoxicity in HeLa cells, with IC50 values of 63.03 \u03bcg\/mL, 33.79 \u03bcg\/mL, and 38.38 \u03bcg\/mL, respectively. Due to their lower IC50 values, the EUD and EUA fractions were selected for further investigation. EUA and EUD inhibited cell migration at all the time points tested and altered the cell cycle. Twenty-eight compounds were tentatively identified in E. uniflora L. leaf extracts based on the interpretation of their fragmentation patterns and molecular formulas obtained from mass spectrometry. Conclusions: The EUD and EUA extracts appear to modulate the metabolism of cervical cancer cells, leading to cell cycle arrest and inhibition of cell migration. Flavonoids and other phenolic compounds are likely responsible for these observed biological effects.<\/jats:p>","DOI":"10.3390\/ph18081199","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T14:51:46Z","timestamp":1755183106000},"page":"1199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Eugenia uniflora L.: Analysis of Chemical Profile and Cytotoxic Action on Tumor (HeLa) and Non-Tumor Cells (NIH\/3T3)"],"prefix":"10.3390","volume":"18","author":[{"given":"Let\u00edcia M. R.","family":"Pescinelli","sequence":"first","affiliation":[{"name":"Research Laboratory of Natural Products and Bioactive Molecules, (Lab Nat\u2014UFF) Nova Friburgo Health Institute, Fluminense Federal University\u2014UFF, Nova Friburgo 28625-650, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena Fran\u00e7a","family":"Longue","sequence":"additional","affiliation":[{"name":"Research Laboratory of Natural Products and Bioactive Molecules, (Lab Nat\u2014UFF) Nova Friburgo Health Institute, Fluminense Federal University\u2014UFF, Nova Friburgo 28625-650, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovana G. F. V.","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Research Laboratory of Natural Products and Bioactive Molecules, (Lab Nat\u2014UFF) Nova Friburgo Health Institute, Fluminense Federal University\u2014UFF, Nova Friburgo 28625-650, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2631-1849","authenticated-orcid":false,"given":"J\u00falio C.","family":"Thurler-J\u00fanior","sequence":"additional","affiliation":[{"name":"Multi-User Biomedical Research Laboratory, Nova Friburgo Health Institute, Fluminense Federal University\u2014UFF, Nova Friburgo 28625-650, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago S.","family":"Charret","sequence":"additional","affiliation":[{"name":"Research Laboratory of Natural Products and Bioactive Molecules, (Lab Nat\u2014UFF) Nova Friburgo Health Institute, Fluminense Federal University\u2014UFF, Nova Friburgo 28625-650, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9287-9750","authenticated-orcid":false,"given":"Thalya S. R.","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Sciences, Center for Exact Sciences and Technology, State University of North Fluminense Darcy Ribeiro\u2014UENF, Campos dos Goytacazes 28013-602, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana T. M.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Research Laboratory of Natural Products and Bioactive Molecules, (Lab Nat\u2014UFF) Nova Friburgo Health Institute, Fluminense Federal University\u2014UFF, Nova Friburgo 28625-650, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo J. C.","family":"Vieira","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Sciences, Center for Exact Sciences and Technology, State University of North Fluminense Darcy Ribeiro\u2014UENF, Campos dos Goytacazes 28013-602, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5620-8095","authenticated-orcid":false,"given":"Lucas S.","family":"Abreu","sequence":"additional","affiliation":[{"name":"Natural Products Chemistry Laboratory, Institute of Chemistry, Fluminense Federal University\u2014UFF, Niteroi 24210-201, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9009-1190","authenticated-orcid":false,"given":"Vinicius D. B.","family":"Pascoal","sequence":"additional","affiliation":[{"name":"Research Laboratory of Natural Products and Bioactive Molecules, (Lab Nat\u2014UFF) Nova Friburgo Health Institute, Fluminense Federal University\u2014UFF, Nova Friburgo 28625-650, RJ, Brazil"},{"name":"Multi-User Biomedical Research Laboratory, Nova Friburgo Health Institute, Fluminense Federal University\u2014UFF, Nova Friburgo 28625-650, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4234-4843","authenticated-orcid":false,"given":"Aislan C. R. F.","family":"Pascoal","sequence":"additional","affiliation":[{"name":"Research Laboratory of Natural Products and Bioactive Molecules, (Lab Nat\u2014UFF) Nova Friburgo Health Institute, Fluminense Federal University\u2014UFF, Nova Friburgo 28625-650, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Naeem, A., Hu, P., Yang, M., Zhang, J., Liu, Y., Zhu, W., and Zheng, Q. (2022). Natural Products as Anticancer Agents: Current Status and Future Perspectives. Molecules, 27.","DOI":"10.3390\/molecules27238367"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pereira, M.T.M., Charret, T.S., Wermelinger, G.F., Nogueira, T.S.R., Robbs, B.K., Castiglione, R.C., Sim\u00f5es, R.L., Machado, R.L.D., Vieira, I.J.C., and Abreu, L.S. (2024). Evaluation of the Antiproliferative Potential of yellow Jaboticaba (Myrciaria glazioviana) extracts against Human Cervical Cancer (HeLa cells line) and the Analysis of their Chemical Composition by HPLC-HRESIMS. Chem. Biodivers., 21.","DOI":"10.1002\/cbdv.202301467"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dre\u021bcanu, G., Iuhas, C.I., and Diaconeasa, Z. (2021). The involvement of natural polyphenols in the chemoprevention of cervical cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168812"},{"key":"ref_5","unstructured":"HPV (2024, May 06). Instituto Nacional de C\u00e2ncer\u2014INCA, Available online: https:\/\/www.gov.br\/inca\/pt-br\/acesso-a-informacao\/perguntas-frequentes\/hpv."},{"key":"ref_6","unstructured":"(2025, April 27). International Agency for Research on Cancer (IARC). Available online: https:\/\/www.iarc.who.int\/cancer-type\/cervical-cancer\/."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/path.1706","article-title":"Molecular mechanisms of drug resistance","volume":"205","author":"Longley","year":"2005","journal-title":"J. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1016\/j.ejca.2014.04.014","article-title":"Review of therapeutic drug monitoring of anticancer drugs part 1\u2014Cytotoxics","volume":"50","author":"Paci","year":"2014","journal-title":"Eur. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrc706","article-title":"Multidrug resistance in cancer: Role of ATP\u2013dependent transporters","volume":"2","author":"Gottesman","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/nrc2789","article-title":"ABC transporters in cancer: More than just drug efflux pumps","volume":"10","author":"Fletcher","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/nature12624","article-title":"Tumour heterogeneity and cancer cell plasticity","volume":"501","author":"Meacham","year":"2013","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000443404","article-title":"Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents","volume":"25","author":"Cragg","year":"2016","journal-title":"Med. Princ. Pract."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: Advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_14","first-page":"e17267","article-title":"N Antineoplastic potential of the aqueous crude extract of Eugenia uniflora L. In human cervical cancer","volume":"54","author":"Pinheiro","year":"2018","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_15","first-page":"1083","article-title":"Tannins and flavonoids from the flowers of Eugenia uniflora (myrtaceae)","volume":"45","author":"Monteiro","year":"2022","journal-title":"Quim. Nova"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"623940","DOI":"10.1155\/2012\/623940","article-title":"Analysis of flavonoids from Eugenia uniflora leaves and its protective effect against murine sepsis","volume":"2012","author":"Rattmann","year":"2012","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sharma, A., Shahzad, B., Rehman, A., Bhardwaj, R., Landi, M., and Zheng, B. (2019). Response of Phenylpropanoid Pathway and the Role of Polyphenols in Plants under Abiotic Stress. Molecules, 24.","DOI":"10.3390\/molecules24132452"},{"key":"ref_18","first-page":"10048","article-title":"Total (poly)phenol analysis by the Folin-Ciocalteu assay as an anti-inflammatory biomarker in biological samples","volume":"64","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_19","first-page":"419","article-title":"M\u00e9todo de Folin Ciocalteau adaptado para quantificar polifen\u00f3is em extratos de erva-mate","volume":"13","author":"Lazzarotto","year":"2020","journal-title":"Movimenta"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Alves, T.P., Pereira, M.T.M., Charret, T.S., Thurler-J\u00fanior, J.C., Wermelinger, G.F., Baptista, A.R., Robbs, B.K., Sawaya, A.C.H.F., Pascoal, V.D.B., and Cristina Pascoal, A.C.R.F. (2022). Evaluation of the Antiproliferative Potential of Eugenia pyriformis Leaves in Cervical Cancer Cells. Chem. Biodivers., 19.","DOI":"10.1002\/cbdv.202200114"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.fct.2018.07.057","article-title":"Purple pitanga fruit (Eugenia uniflora L.) protects against oxidative stress and increase the lifespan in Caenorhabditis elegans via the DAF-16\/FOXO pathway","volume":"120","author":"Tambara","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1039\/D1QO01629F","article-title":"Eugenunilones A\u2013H: Rearranged sesquiterpenoids from Eugenia uniflora","volume":"9","author":"Chen","year":"2022","journal-title":"Org. Chem. Front."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"113699","DOI":"10.1016\/j.phytochem.2023.113699","article-title":"Eugenilones A-N: Sesquiterpenoids from the fruits of Eugenia uniflora","volume":"211","author":"Chen","year":"2023","journal-title":"Phytochemistry"},{"key":"ref_24","unstructured":"Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (2024, May 06). An Overview of the Cell Cycle, Molecular Biology of the Cell, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK26869\/."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Malumbres, M. (2014). Cyclin-dependent kinases. Genome Biol., 15.","DOI":"10.1186\/gb4184"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5504","DOI":"10.7150\/jca.32628","article-title":"Cyclin-Dependent Kinases 4\/6 Inhibitors in Breast Cancer: Current Status, Resistance, and Combination Strategies","volume":"10","author":"Niu","year":"2019","journal-title":"J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1242\/dev.091744","article-title":"Cdks, cyclins and CKIs: Roles beyond cell cycle regulation","volume":"140","author":"Lim","year":"2013","journal-title":"Development"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zari, A.T., Zari, T.A., and Hakeem, K.R. (2021). Anticancer Properties of Eugenol: A Review. Molecules, 26.","DOI":"10.3390\/molecules26237407"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jep.2018.12.011","article-title":"Composition, antioxidant capacity and cytotoxic activity of Eugenia uniflora L. chemotype-oils from the Amazon","volume":"232","author":"Figueiredo","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Monteiro, J.R.B., Ardisson, J.S., Athaydes, B.R., Gon\u00e7alves, R.C.R., Rodrigues, R.P., Kuster, R.M., and Kitagawa, R.R. (2019). Anti-Helicobacter pylori and Anti-inflammatory Properties of Eugenia uniflora L.. Braz. Arch. Biol. Technol., 62.","DOI":"10.1590\/1678-4324-2019180285"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Correia, V.T.V., Silva, P.R., Ribeiro, C.M.S., Ramos, A.L.C.C., Mazzinghy, A.C.D.C., Silva, V.D.M., J\u00fanior, A.H.O., Nunes, B.V., Vieira, A.L.S., and Ribeiro, L.V. (2022). An Integrative Review on the Main Flavonoids Found in Some Species of the Myrtaceae Family: Phytochemical Characterization. Health Benefits and Development of Products. Plants, 11.","DOI":"10.3390\/plants11202796"},{"key":"ref_32","first-page":"370","article-title":"Antiproliferative Effect of Ethanolic Extract Eugenia uniflora Lam. Leaves on T47D Cells","volume":"3","author":"Ismiyati","year":"2012","journal-title":"Indones. J. Cancer Chemoprev."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chen, W., Shen, X., Ma, L., Chen, R., Yuan, Q., Zheng, Y., Li, C., and Peng, G. (2020). Phenolic Compounds from Polygonum chinense Induce Growth Inhibition and Apoptosis of Cervical Cancer SiHa Cells. BioMed Res. Int., 2020.","DOI":"10.1155\/2020\/8868508"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ma, C.H., Zhao, J.F., Zhang, X.G., Ding, C.H., Hao, H.H., Ji, Y.H., Li, L.P., Guo, Z.T., and Liu, W.S. (2023). Discovery of ellagic acid as a competitive inhibitor of Src homology phosphotyrosyl phosphatase 2 (SHP2) for cancer treatment: In vitro and in silico study. Int. J. Biol. Macromol., 254.","DOI":"10.1016\/j.ijbiomac.2023.127845"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Oriola, A.O., Miya, G.M., Singh, M., and Oyedeji, A.O. (2023). Flavonol Glycosides from Eugenia uniflora Leaves and Their In Vitro Cytotoxicity, Antioxidant and Anti-Inflammatory Activities. Sci. Pharm., 91.","DOI":"10.3390\/scipharm91030042"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9770","DOI":"10.1080\/07391102.2022.2146202","article-title":"In-silico analysis reveals Quinic acid as a multitargeted inhibitor against Cervical Cancer","volume":"41","author":"Ahmad","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"477","DOI":"10.2174\/1568011054866973","article-title":"Sesquiterpenes: Natural products that decrease cancer growth","volume":"5","author":"Modzelewska","year":"2005","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12935-019-0868-0","article-title":"Effect of Gallic acid in potentiating chemotherapeutic effect of Paclitaxel in HeLa cervical cancer cells","volume":"19","author":"Aborehab","year":"2019","journal-title":"Cancer Cell Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3408","DOI":"10.1080\/02648725.2022.2122303","article-title":"Pharmacological insights into the multifaceted biological properties of quinic acid","volume":"40","author":"Benali","year":"2024","journal-title":"Biotechnol. Genet. Eng. Rev."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/8\/1199\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:27:21Z","timestamp":1760034441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/8\/1199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,14]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ph18081199"],"URL":"https:\/\/doi.org\/10.3390\/ph18081199","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,14]]}}}