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Lobaric Acid Exhibits Anticancer Potential by Modulating the Wnt/β-Catenin Signaling Pathway in MCF-7 Cells
Şeyda Nur Kalın1,2, Kübra Nur Bayındırlı1,3, Emine Toraman1
1Department of Molecular Biology and Genetics, Science Faculty, Atatürk University, Erzurum, Turkey.
Abstract:
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 IC50 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.
Insights
Lobaric acid, a lichen metabolite, shows potential as a breast cancer treatment by inducing apoptosis and inhibiting the Wnt/β-catenin pathway. This natural compound may offer a new therapeutic avenue with low side effects.
Area of Science:
- Natural Product Chemistry
- Cancer Biology
- Molecular Pharmacology
Background:
- Lichen secondary metabolites possess anticancer properties, targeting pathways like Wnt/β-catenin.
- The Wnt/β-catenin pathway is crucial in oncogenesis, proliferation, and metastasis.
- Lobaric acid (LA) is a lichen metabolite with unexplored anticancer mechanisms in breast cancer.
Purpose of the Study:
- To investigate the anticancer effects of lobaric acid (LA) on MCF-7 breast cancer cells.
- To elucidate the molecular mechanism of LA, focusing on apoptosis, migration, and the Wnt/β-catenin signaling pathway.
Main Methods:
- XTT assay to determine cell viability and IC50.
- Flow cytometry, qPCR, and Western blot to assess apoptosis and pathway modulation.
- Analysis of β-catenin and GSK3-β protein expression.
Main Results:
- Lobaric acid exhibited dose- and time-dependent cytotoxicity against MCF-7 cells with an IC50 of 44.21 μg/mL at 48h.
- LA significantly increased apoptosis in breast cancer cells.
- LA suppressed the Wnt/β-catenin pathway by upregulating GSK3-β and inhibiting β-catenin.
Conclusions:
- Lobaric acid demonstrates significant anticancer activity against breast cancer cells.
- LA induces apoptosis and inhibits cell migration by targeting the Wnt/β-catenin pathway.
- Lobaric acid is a promising natural compound for breast cancer therapeutic development.
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