{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T18:53:31Z","timestamp":1788288811325,"version":"build-2803163510"},"reference-count":28,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brazil","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cervical cancer remains a significant global health concern, causing more than 300,000 deaths annually. Erythrina velutina, a tree native to north-eastern Brazil, contains bioactive alkaloids with potential anticancer properties. This study aimed to characterize the alkaloid-enriched fraction of Erythrina velutina leaves and investigate the effects of the alkaloid erythraline on apoptosis and cell cycle in SiHa cervical cancer cells. Using Gas Chromatography\u2013Mass Spectrometry (GC-MS), six alkaloids, including erythraline, were identified. Cytotoxicity was assessed through proliferation assays on SiHa cells and peripheral blood mononuclear cells (PBMCs). Apoptosis and cell cycle analyses were performed using flow cytometry, and in silico virtual screening identified potential protein targets of erythraline. Erythraline showed time- and concentration-dependent inhibitory effects on SiHa cell proliferation, with significant cytotoxicity observed at 50 \u00b5g\/mL. Morphological changes, chromatin condensation, and increased apoptotic cell percentages confirmed the induction of caspase-independent apoptosis. Erythraline also induced G2\/M cell cycle arrest, with 22% of cells in the G2\/M phase compared with 7.25% in the untreated controls. In silico analysis identified polyamine oxidase, pyruvate kinase M2, and tankyrase as potential targets that contribute to the antitumor activity of erythraline. These findings suggest that erythraline is a promising candidate for anticancer therapy, warranting further investigation.<\/jats:p>","DOI":"10.3390\/ijms26104627","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T10:58:07Z","timestamp":1747047487000},"page":"4627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Apoptosis and G2\/M Phase Cell Cycle Arrest Induced by Alkaloid Erythraline Isolated from Erythrina velutina in SiHa Cervical Cancer Cell"],"prefix":"10.3390","volume":"26","author":[{"given":"Cleine Aglacy Nunes","family":"Miranda","sequence":"first","affiliation":[{"name":"Postgraduate Program in Development and Technological Innovation in Medicines, Federal University of Rio Grande do Norte, Natal 52171-900, RN, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7085-8788","authenticated-orcid":false,"given":"Amaxsell Thiago Barros de","family":"Souza","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Sciences Applied to Women\u2019s Health, Federal University of Rio Grande do Norte, Natal 59012-310, RN, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Katarina Menezes da Cruz","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Federal University of Rio Grande do Norte, Natal 59064-741, RN, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuelly","family":"Bernardes-Oliveira","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Development and Technological Innovation in Medicines, Federal University of Rio Grande do Norte, Natal 52171-900, RN, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2252-1221","authenticated-orcid":false,"given":"Hugo Alexandre Oliveira","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Federal University of Rio Grande do Norte, Natal 59064-741, RN, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7685-9618","authenticated-orcid":false,"given":"Euz\u00e9bio Guimar\u00e3es","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, RN, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-6871","authenticated-orcid":false,"given":"Thais","family":"Guaratini","sequence":"additional","affiliation":[{"name":"Lychnoflora Research and Development in Natural Products LTDA, Ribeir\u00e3o Preto 14040-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6140-1794","authenticated-orcid":false,"given":"Norma","family":"Lucena-Silva","sequence":"additional","affiliation":[{"name":"Department of Immunology, Aggeu Magalh\u00e3es Institute, Oswaldo Cruz Foundation, Recife 50670-465, PE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0184-2061","authenticated-orcid":false,"given":"Ricardo Ney","family":"Cobucci","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Sciences Applied to Women\u2019s Health, Federal University of Rio Grande do Norte, Natal 59012-310, RN, Brazil"},{"name":"Postgraduate Program in Biotechnology, Potiguar University, Natal 59056-000, RN, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel Brandt","family":"Giordani","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, RN, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1344-0078","authenticated-orcid":false,"given":"Janaina Cristiana de Oliveira","family":"Crispim","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Development and Technological Innovation in Medicines, Federal University of Rio Grande do Norte, Natal 52171-900, RN, Brazil"},{"name":"Postgraduate Program in Sciences Applied to Women\u2019s Health, Federal University of Rio Grande do Norte, Natal 59012-310, RN, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e191","DOI":"10.1016\/S2214-109X(19)30482-6","article-title":"Estimates of incidence and mortality of cervi-cal cancer in 2018: A worldwide analysis","volume":"8","author":"Arbyn","year":"2020","journal-title":"Lancet Glob. 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