Kalın Şeyda Nur, Bayındırlı Kübra Nur, Toraman Emine, Günaydın Şükran, Keleş Fatmanur, Altay Ahmet, Budak Harun
Department of Molecular Biology and Genetics, Science Faculty, Atatürk University, Erzurum, Turkey.
Department of Chemistry, Faculty of Science and Arts, Erzincan Binali Yıldırım University, Erzincan, Turkey.
Pharmacol Res Perspect. 2025 Aug;13(4):e70142. doi: 10.1002/prp2.70142.
Lichen secondary metabolites with many remarkable biological activities are used in cancer treatments due to their low side effects and high anticancer potential. In particular, these metabolites constitute an interesting research area in cancer treatments due to their potential to induce apoptosis and suppress metastasis by inhibiting cancer-related signaling pathways. The Wnt/β-catenin signaling pathway plays a role in important biological processes such as oncogenesis, cell cycle regulation, cell proliferation, metastasis, differentiation, apoptosis, and drug resistance. Therefore, inhibition of this pathway is a potential target in cancer therapies. There is no detailed study explaining the potential anticancer molecular mechanism of the lichen secondary metabolite lobaric acid (LA) on breast cancer. Here, it is aimed to investigate the effect of LA on viability, apoptosis, and migration in MCF-7 cells and to elucidate the relationship between the potential anticancer effect and the Wnt/β-catenin signaling pathway. The dose- and time-dependent viability of LA-treated MCF-7 cells was evaluated by XTT assay, and the IC value was determined as 44.21 μg/mL at 48 h. LA increased the apoptotic cell population, as shown by flow cytometry analysis, qPCR, and Western blot results. LA inhibited β-catenin by inducing GSK3-β protein expression, thereby suppressing Wnt/β-catenin target genes. LA might be a natural active compound candidate for breast cancer treatment.
地衣次生代谢产物具有许多显著的生物活性，因其副作用低且抗癌潜力高而被用于癌症治疗。特别是，这些代谢产物因其通过抑制癌症相关信号通路诱导细胞凋亡和抑制转移的潜力，在癌症治疗中构成了一个有趣的研究领域。Wnt/β-连环蛋白信号通路在肿瘤发生、细胞周期调控、细胞增殖、转移、分化、凋亡和耐药性等重要生物学过程中发挥作用。因此，抑制该通路是癌症治疗的一个潜在靶点。目前尚无详细研究解释地衣次生代谢产物洛巴酸（LA）对乳腺癌的潜在抗癌分子机制。在此，旨在研究LA对MCF-7细胞活力、凋亡和迁移的影响，并阐明潜在抗癌作用与Wnt/β-连环蛋白信号通路之间的关系。通过XTT法评估LA处理的MCF-7细胞的剂量和时间依赖性活力，在48小时时IC值确定为44.21μg/mL。流式细胞术分析、qPCR和蛋白质印迹结果表明，LA增加了凋亡细胞群体。LA通过诱导GSK3-β蛋白表达抑制β-连环蛋白，从而抑制Wnt/β-连环蛋白靶基因。LA可能是一种用于乳腺癌治疗的天然活性化合物候选物。
