Related Experiment Video
Updated: Jul 19, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Identification of Bacterial Metabolites Modulating Breast Cancer Cell Proliferation and Epithelial-Mesenchymal
Gyula Ujlaki1, Tünde Kovács1, András Vida1
1Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Abstract:
Breast cancer patients are characterized by the oncobiotic transformation of multiple microbiome communities, including the gut microbiome. Oncobiotic transformation of the gut microbiome impairs the production of antineoplastic bacterial metabolites. The goal of this study was to identify bacterial metabolites with antineoplastic properties. We constructed a 30-member bacterial metabolite library and screened the library compounds for effects on cell proliferation and epithelial-mesenchymal transition. The metabolites were applied to 4T1 murine breast cancer cells in concentrations corresponding to the reference serum concentrations. However, yric acid, glycolic acid, d-mannitol, 2,3-butanediol, and trans-ferulic acid exerted cytostatic effects, and 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, and vanillic acid exerted hyperproliferative effects. Furthermore, 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 2,3-butanediol, and hydrocinnamic acid inhibited epithelial-to-mesenchymal (EMT) transition. We identified redox sets among the metabolites (d-mannitol-d-mannose, 1-butanol-butyric acid, ethylene glycol-glycolic acid-oxalic acid), wherein only one partner within the set (d-mannitol, butyric acid, glycolic acid) possessed bioactivity in our system, suggesting that changes to the local redox potential may affect the bacterial secretome. Of the nine bioactive metabolites, 2,3-butanediol was the only compound with both cytostatic and anti-EMT properties.
Insights
Breast cancer alters the gut microbiome, reducing antineoplastic metabolites. This study identified specific bacterial metabolites, like 2,3-butanediol, that inhibit cancer cell growth and migration.
Area of Science:
- Microbiology
- Oncology
- Metabolomics
Background:
- Breast cancer is linked to gut microbiome dysbiosis, impacting the production of beneficial antineoplastic (cancer-fighting) bacterial metabolites.
- Understanding these microbial metabolites is crucial for developing novel therapeutic strategies against breast cancer.
Purpose of the Study:
- To identify specific bacterial metabolites with antineoplastic properties, including effects on cancer cell proliferation and epithelial-mesenchymal transition (EMT).
Main Methods:
- A library of 30 bacterial metabolites was screened for their effects on 4T1 murine breast cancer cells.
- Compounds were tested at concentrations reflecting reference serum levels to assess impact on cell proliferation and EMT.
Main Results:
- Several metabolites exhibited cytostatic (inhibiting cell growth) or hyperproliferative (promoting cell growth) effects.
- Specific metabolites, including 3-hydroxyphenylacetic acid and 2,3-butanediol, were found to inhibit EMT, a process crucial for cancer metastasis.
- 2,3-butanediol demonstrated both cytostatic and anti-EMT properties, making it a promising candidate.
Conclusions:
- Bacterial metabolites play a significant role in breast cancer progression and can be targeted for therapeutic intervention.
- 2,3-butanediol is a key metabolite with dual action against breast cancer cell proliferation and EMT, warranting further investigation.
More Related Videos
Related Concept Videos
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
02:38Mitogens and the Cell Cycle