{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T21:54:32Z","timestamp":1769550872902,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT), Portugal","doi-asserted-by":"publisher","award":["PTDC\/MED-QUI\/30591\/2017"],"award-info":[{"award-number":["PTDC\/MED-QUI\/30591\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT), Portugal","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT), Portugal","doi-asserted-by":"publisher","award":["SFRH\/BD\/130348\/2017"],"award-info":[{"award-number":["SFRH\/BD\/130348\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT), Portugal","doi-asserted-by":"publisher","award":["022161"],"award-info":[{"award-number":["022161"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Infrastructure Project","award":["PTDC\/MED-QUI\/30591\/2017"],"award-info":[{"award-number":["PTDC\/MED-QUI\/30591\/2017"]}]},{"name":"Infrastructure Project","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"Infrastructure Project","award":["SFRH\/BD\/130348\/2017"],"award-info":[{"award-number":["SFRH\/BD\/130348\/2017"]}]},{"name":"Infrastructure Project","award":["022161"],"award-info":[{"award-number":["022161"]}]},{"name":"FEDER","award":["PTDC\/MED-QUI\/30591\/2017"],"award-info":[{"award-number":["PTDC\/MED-QUI\/30591\/2017"]}]},{"name":"FEDER","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"FEDER","award":["SFRH\/BD\/130348\/2017"],"award-info":[{"award-number":["SFRH\/BD\/130348\/2017"]}]},{"name":"FEDER","award":["022161"],"award-info":[{"award-number":["022161"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Aiming to find Amaryllidaceae alkaloids against breast cancer, including the highly aggressive triple-negative breast cancer, the phytochemical study of Pancratium maritimum was carried out. Several Amaryllidaceae-type alkaloids, bearing scaffolds of the haemanthamine-, homolycorine-, lycorine-, galanthamine-, and tazettine-type were isolated (3\u201311), along with one alkamide (2) and a phenolic compound (1). The antiproliferative effect of compounds (1\u201311) was evaluated by the sulforhodamine B assay against triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468, breast cancer cells MCF-7, and the non-malignant fibroblast (HFF-1) and breast (MCF12A) cell lines. The alkaloids 3, 5, 7, and 11 showed significant growth inhibitory effects against all breast cancer cell lines, with IC50 (half-maximal inhibitory concentration) values ranging from 0.73 to 16.3 \u00b5M. The homolycorine-type alkaloid 7 was selected for further investigation in MDA-MB-231 cells. In the annexin-V assay, compound 7 increased cell death by apoptosis, which was substantiated, in western blot analyses, by the increased expression of the pro-apoptotic protein Bax, and the decreased expression of the anti-apoptotic protein Bcl-xL. Consistently, it further stimulated mitochondrial reactive oxygen species (ROS) generation. The antiproliferative effect of compound 7 was also associated with G2\/M cell cycle arrest, which was supported by an increase in the p21 protein expression levels. In MDA-MB-231 cells, compound 7 also exhibited synergistic effects with conventional chemotherapeutic drugs such as etoposide.<\/jats:p>","DOI":"10.3390\/molecules27185759","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T01:51:57Z","timestamp":1662515517000},"page":"5759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Amaryllidaceae-Type Alkaloids from Pancratium maritimum: Apoptosis-Inducing Effect and Cell Cycle Arrest on Triple-Negative Breast Cancer Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3333-7729","authenticated-orcid":false,"given":"Shirley A. R.","family":"Sancha","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]},{"given":"Adriana V.","family":"Gomes","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laborat\u1f79rio de Microbiologia, Departamento de Ci\u00eancias Biol\u1f79gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1975-1125","authenticated-orcid":false,"given":"Joana B.","family":"Loureiro","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laborat\u1f79rio de Microbiologia, Departamento de Ci\u00eancias Biol\u1f79gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-4939","authenticated-orcid":false,"given":"Luc\u00edlia","family":"Saraiva","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laborat\u1f79rio de Microbiologia, Departamento de Ci\u00eancias Biol\u1f79gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8742-1486","authenticated-orcid":false,"given":"Maria Jos\u00e9 U.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ijc.33588","article-title":"Cancer Statistics for the Year 2020: An Overview","volume":"149","author":"Ferlay","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wu, T.-N., Chen, H.-M., and Shyur, L.-F. (2021). Current Advancements of Plant-Derived Agents for Triple-Negative Breast Cancer Therapy through Deregulating Cancer Cell Functions and Reprogramming Tumor Microenvironment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413571"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1016\/j.drudis.2021.03.011","article-title":"The Emerging Role of Immune Checkpoint Inhibitors in the Treatment of Triple-Negative Breast Cancer","volume":"26","author":"Singh","year":"2021","journal-title":"Drug Discov. 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