{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["20(2)"],"submitter":["Aghaei M"],"pubmed_abstract":["In phytochemical analysis, Jacein derivatives: 5,7,4'-trihydroxy-3,6,3'-trimethoxyflavone-7(β)-D-glucopyranoside (<b>1</b>), and 3-demethyljacein: 3,5,7,4'-tetrahydroxy-6,3'-dimethoxyflavone-7(β)-D-glucopyranoside (<b>2</b>) were isolated from <i>Campylopus schmidii (C. schmidii)</i> for the first time. The structures were determined by interpretation of NMR, UV, and Mass spectra. To check the roles of ER stress and consequent apoptosis in MCF-7 cell by these compounds, UPR signaling pathway was further examined by analysis of expression of ER stress-related genes. In MTT assay, compounds <b>1</b>-<b>2</b> showed cytotoxicity activity against MCF-7 (A) and MDA-MB cells (B) with IC<sub>50</sub> values (μM) of <b>1</b>) 60.04 ± 7.98 (A), and > 200 (B); <b>2</b>) 42.89 ± 1.91 (A), and 85.31 ± 2.68 (B). The Annexin/PI flow cytometry apoptosis of tested compounds <b>1-2</b> was increased significantly in a dose-dependent manner. For example, MCF-7 treatment at the concentration of 100 μM of compounds <b>1</b>, <b>2</b> resulted in total apoptosis (early + late) of 42.04 (18.1 + 24.0), and 66.49 (2.7 + 63.8)%, respectively. Fluorescence microscopy analysis detected an increased protein aggregation, indicating induced ER stress with a marked increase in XBP-1, sXBP-1, ATF-4, and CHoP compared to untreated cells. <i>In-silico</i> characterization, suggested that Adenosine diphosphate site (A-site) and quercetin site (Q-Site) in IRE1a enzyme are both available interacting sites of a target for the investigated ligands but with different strengths of interactions. The results indicated that the ligand∼A-Site complexes are stronger than the ligand∼Q-Site complexes, but the already available ADP ligand in cells does not allow other ligands to interact with the A-Site and cause them to bond in Q-Site."],"journal":["Iranian journal of pharmaceutical research : IJPR"],"pagination":["417-432"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8457730"],"repository":["biostudies-literature"],"pubmed_title":["6-Methoxylated Flavonoids: Jacein, and 3-demethyljacein from <i>Centaurea schmidii</i> with Their Endoplasmic Reticulum Stress and Apoptotic Cell Death in Breast Cancer Cells Along with <i>In-silico</i> Analysis."],"pmcid":["PMC8457730"],"pubmed_authors":["Mirzaei M","Mahboodi R","Fallah M","Ghanadian M","Aghaei M"],"additional_accession":[]},"is_claimable":false,"name":"6-Methoxylated Flavonoids: Jacein, and 3-demethyljacein from <i>Centaurea schmidii</i> with Their Endoplasmic Reticulum Stress and Apoptotic Cell Death in Breast Cancer Cells Along with <i>In-silico</i> Analysis.","description":"In phytochemical analysis, Jacein derivatives: 5,7,4'-trihydroxy-3,6,3'-trimethoxyflavone-7(β)-D-glucopyranoside (<b>1</b>), and 3-demethyljacein: 3,5,7,4'-tetrahydroxy-6,3'-dimethoxyflavone-7(β)-D-glucopyranoside (<b>2</b>) were isolated from <i>Campylopus schmidii (C. schmidii)</i> for the first time. The structures were determined by interpretation of NMR, UV, and Mass spectra. To check the roles of ER stress and consequent apoptosis in MCF-7 cell by these compounds, UPR signaling pathway was further examined by analysis of expression of ER stress-related genes. In MTT assay, compounds <b>1</b>-<b>2</b> showed cytotoxicity activity against MCF-7 (A) and MDA-MB cells (B) with IC<sub>50</sub> values (μM) of <b>1</b>) 60.04 ± 7.98 (A), and > 200 (B); <b>2</b>) 42.89 ± 1.91 (A), and 85.31 ± 2.68 (B). The Annexin/PI flow cytometry apoptosis of tested compounds <b>1-2</b> was increased significantly in a dose-dependent manner. For example, MCF-7 treatment at the concentration of 100 μM of compounds <b>1</b>, <b>2</b> resulted in total apoptosis (early + late) of 42.04 (18.1 + 24.0), and 66.49 (2.7 + 63.8)%, respectively. Fluorescence microscopy analysis detected an increased protein aggregation, indicating induced ER stress with a marked increase in XBP-1, sXBP-1, ATF-4, and CHoP compared to untreated cells. <i>In-silico</i> characterization, suggested that Adenosine diphosphate site (A-site) and quercetin site (Q-Site) in IRE1a enzyme are both available interacting sites of a target for the investigated ligands but with different strengths of interactions. The results indicated that the ligand∼A-Site complexes are stronger than the ligand∼Q-Site complexes, but the already available ADP ligand in cells does not allow other ligands to interact with the A-Site and cause them to bond in Q-Site.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021","modification":"2025-05-29T20:29:43.209Z","creation":"2022-02-11T11:28:21.256Z"},"accession":"S-EPMC8457730","cross_references":{"pubmed":["34567171"],"doi":["10.22037/ijpr.2020.113895.14548"]}}