Atranorin suppresses the LUCAT1/STAT3 axis to induce ferroptotic cell death in ovarian cancer
Molecular Biology Reports, cilt.53, sa.1, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 53 Sayı: 1
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s11033-026-12442-1
- Dergi Adı: Molecular Biology Reports
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
- Anahtar Kelimeler: Atranorin, Ferroptosis, Long non-coding RNA, LUCAT1, Ovarian cancer, STAT3
- Ankara Üniversitesi Adresli: Evet
Özet
Objective: Ovarian cancer remains the most lethal gynecological malignancy and represents a major cause of cancer-related mortality among women worldwide. Despite advances in therapeutic strategies, treatment efficacy is frequently limited by systemic toxicity, chemoresistance, and disease recurrence, highlighting the urgent need for novel, mechanism-based targeted therapies with improved safety profiles. In the present study, we investigated the anti-cancer activity of atranorin (ATR), a naturally derived small-molecule compound, with a particular focus on its ability to induce ferroptosis by modulation of the LUCAT1/STAT3 signaling axis. Methods: Human ovarian cancer cell lines (OVCAR-3 and SKOV-3) and normal ovarian surface epithelial (OSE) cells were employed to evaluate cytotoxic selectivity and mechanistic effects. Results: ATR selectively inhibited proliferation of ovarian cancer cells while exerting minimal cytotoxicity toward normal OSE cells. Mechanistic analyses demonstrated that ATR significantly suppressed LUCAT1 and STAT3 expression at both mRNA and protein levels, as confirmed by qRT-PCR and Western blotting. Concomitantly, ATR upregulated ferroptosis-related genes and proteins. Biochemical assessments revealed increased intracellular reactive oxygen species (ROS), elevated malondialdehyde (MDA) and iron accumulation, and depletion of glutathione (GSH), collectively indicating activation of ferroptotic cell death. Furthermore, ATR significantly impaired migratory and invasive capacities of ovarian cancer cells. Collectively, our findings identify ATR as a compound capable of inducing biochemical features consistent with ferroptosis in ovarian cancer through suppression of the LUCAT1/STAT3 axis. Discussion: These results uncover a previously uncharacterized mechanistic pathway underlying ATR-mediated anti-tumor effect and support its potential development as a targeted therapeutic candidate for ovarian cancer management.