{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE341nnn/GSE341147/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE341147"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Magnolol triggers ferroptosis in triple-negative breast cancer through modulation of the ETS2/SLC7A11/GPX4 signaling axis","description":"Background: Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation (LPO), represents a promising therapeutic strategy. Magnolia officinalis, a traditional herb for resolving dampness and phlegm, is known to modulate cellular metabolism. While magnolol (MAG), a bioactive neolignan from Magnolia officinalis, shows anti-TNBC activity, its role in inducing ferroptosis remains unexplored. Methods: Anti-TNBC effects of MAG were assessed in MDA-MB-231 and 4T1 cells via viability, apoptosis, and ferroptosis assays (intracellular Fe²⁺, LPO, GSH). Target identification employed network pharmacology, RNA-seq, surface plasmon resonance, and pull-down assays. Mechanisms were validated using siRNA/overexpression, Co-IP, and immunofluorescence. In vivo efficacy was evaluated in xenograft models. Results: MAG inhibited proliferation and induced apoptosis and ferroptosis in TNBC cells, evidenced by elevated Fe²⁺ and lipid peroxidation, depleted GSH, downregulated SLC7A11/GPX4, and mitochondrial shrinkage effects reversed by ferroptosis inhibitors. MAG directly bound and suppressed transcription factor ETS2. ETS2 knockdown sensitized cells to MAG-induced ferroptosis, while its overexpression restored SLC7A11/GPX4 expression and conferred resistance. Mechanistically, ETS2 transcriptionally regulated SLC7A11, and MAG enhanced ETS2-SLC7A11 protein interaction. In vivo, MAG significantly suppressed tumor growth with low toxicity and downregulated ETS2, SLC7A11, and GPX4. Conclusions: MAG induces ferroptosis in MDA-MB-231 cells, which may be mediated by targeting the ETS2/SLC7A11/GPX4 signaling axis, providing mechanistic insights into its anti-TNBC activity.","dates":{"publication":"2026/07/27"},"accession":"GSE341147","cross_references":{"GSM":["GSM9900988","GSM9900983","GSM9900987","GSM9900986","GSM9900985","GSM9900984"],"GPL":["33758"],"GSE":["341147"],"taxon":["Homo sapiens"],"PMID":["[42602283]"]}}