Akademik Veri Yönetim Sistemi
7th Eurasia Biochemical Approaches & Technologies (EBAT), Antalya, Türkiye, 6 - 09 Kasım 2025, ss.103, (Özet Bildiri)
Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor that promotes proliferation, metastasis, and immune evasion through its overexpression.1 In recent years, it has been reported that some STAT3 inhibitors also exert an inhibitory effect on cytosolic thioredoxin reductase 1 (TrxR1), while some TrxR1 inhibitors block STAT3-dependent transcriptional activity.2,3 The high expression of TrxR1 in many cancer types makes this relationship even more meaningful, and elucidating the TrxR1–STAT3 interaction is considered an important target for the development of new therapeutic strategies. In this context, natural products attract attention due to their capacity to affect multiple molecular targets; secondary metabolites produced by lichens, in particular, offer potent antitumor potential by inhibiting the growth and progression of cancer cells due to their antioxidant, cytotoxic, pro-apoptotic, and anti-proliferative properties.4 This study aimed to investigate the anticancer potential of the lichen secondary metabolite evernic acid (EA) by targeting the STAT3–TrxR1 pathway in human breast cancer (MCF-7) cells. EA, evaluated by the XTT assay, exhibited dose- (0–100 μg/ml) and time-(24 and 48 h) dependent cytotoxicity in MCF 7 cells, with an IC50 value of 33.79 μg/ml at 52 h. Transwell migration assay results showed that EA significantly inhibited migration in MCF-7 cells (p<0.001). TrxR1 enzymatic activity was significantly inhibited in EA-treated MCF-7 cells (p<0.05). According to quantitative Real Time PCR results, EA significantly down-regulated the gene expressions of IL-6 (p<0.05), JAK1 (p<0.05), JAK2 (p<0.001), and STAT3 (p<0.01) in MCF-7 cells, increased the expression of IFN-γ (p<0.001) and TNF-α (p<0.01) genes. Western blot analysis results showed that EA treatment significantly suppressed p-JAK1, p-JAK2, and p-STAT3 protein expressions (p<0.05). The findings indicated that the TrxR1 inhibitor EA suppresses STAT3 activity by inhibiting the JAK/STAT pathway. Consequently, EA has both anticancer and immunomodulatory potential in breast cancer via the STAT3-TrxR1 interaction. This study was funded by the Coordination Unit of Scientific Research Projects of Atatürk University (ATAUNI-BAP) (Project number: FDK-2019-7204) and the Scientific and Technological Research Council of Turkey (TÜBİTAK) (Project number: 123C291).