{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sancha SAR"],"funding":["Fundação para a Ciência e Tecnologia"],"pagination":["5759"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9501014"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(18)"],"pubmed_abstract":["Aiming to find Amaryllidaceae alkaloids against breast cancer, including the highly aggressive triple-negative breast cancer, the phytochemical study of <i>Pancratium maritimum</i> was carried out. Several Amaryllidaceae-type alkaloids, bearing scaffolds of the haemanthamine-, homolycorine-, lycorine-, galanthamine-, and tazettine-type were isolated (<b>3</b>-<b>11</b>), along with one alkamide (<b>2</b>) and a phenolic compound (<b>1</b>). The antiproliferative effect of compounds (<b>1</b>-<b>11</b>) 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 <b>3</b>, <b>5</b>, <b>7</b>, and <b>11</b> showed significant growth inhibitory effects against all breast cancer cell lines, with IC<sub>50</sub> (half-maximal inhibitory concentration) values ranging from 0.73 to 16.3 µM. The homolycorine-type alkaloid <b>7</b> was selected for further investigation in MDA-MB-231 cells. In the annexin-V assay, compound <b>7</b> 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 <b>7</b> 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 <b>7</b> also exhibited synergistic effects with conventional chemotherapeutic drugs such as etoposide."],"journal":["Molecules (Basel, Switzerland)"],"pubmed_title":["Amaryllidaceae-Type Alkaloids from <i>Pancratium maritimum</i>: Apoptosis-Inducing Effect and Cell Cycle Arrest on Triple-Negative Breast Cancer Cells."],"pmcid":["PMC9501014"],"funding_grant_id":["UIDB/50006/2020","SFRH/BD/130348/2017","PTDC/MED-QUI/30591/2017"],"pubmed_authors":["Loureiro JB","Ferreira MJU","Sancha SAR","Gomes AV","Saraiva L"],"additional_accession":[]},"is_claimable":false,"name":"Amaryllidaceae-Type Alkaloids from <i>Pancratium maritimum</i>: Apoptosis-Inducing Effect and Cell Cycle Arrest on Triple-Negative Breast Cancer Cells.","description":"Aiming to find Amaryllidaceae alkaloids against breast cancer, including the highly aggressive triple-negative breast cancer, the phytochemical study of <i>Pancratium maritimum</i> was carried out. Several Amaryllidaceae-type alkaloids, bearing scaffolds of the haemanthamine-, homolycorine-, lycorine-, galanthamine-, and tazettine-type were isolated (<b>3</b>-<b>11</b>), along with one alkamide (<b>2</b>) and a phenolic compound (<b>1</b>). The antiproliferative effect of compounds (<b>1</b>-<b>11</b>) 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 <b>3</b>, <b>5</b>, <b>7</b>, and <b>11</b> showed significant growth inhibitory effects against all breast cancer cell lines, with IC<sub>50</sub> (half-maximal inhibitory concentration) values ranging from 0.73 to 16.3 µM. The homolycorine-type alkaloid <b>7</b> was selected for further investigation in MDA-MB-231 cells. In the annexin-V assay, compound <b>7</b> 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 <b>7</b> 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 <b>7</b> also exhibited synergistic effects with conventional chemotherapeutic drugs such as etoposide.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2024-10-19T08:21:13.612Z","creation":"2024-10-19T08:21:13.612Z"},"accession":"S-EPMC9501014","cross_references":{"pubmed":["36144504"],"doi":["10.3390/molecules27185759"]}}