Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness

Edit Mikó, András Vida, Tünde Kovács, Gyula Ujlaki, György Trencsényi, Judit Márton, Zsanett Sári, Patrik Kovács, Anita Boratkó, Zoltán Hujber, Tamás Csonka, Péter Antal-Szalmás, Mitsuhiro Watanabe, Imre Gombos, Balazs Csoka, Borbála Kiss, László Vígh, Judit Szabó, Gábor Méhes, Anna SebestyénJames J. Goedert, Péter Bai

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Our study aimed at finding a mechanistic relationship between the gut microbiome and breast cancer. Breast cancer cells are not in direct contact with these microbes, but disease could be influenced by bacterial metabolites including secondary bile acids that are exclusively synthesized by the microbiome and known to enter the human circulation. In murine and bench experiments, a secondary bile acid, lithocholic acid (LCA) in concentrations corresponding to its tissue reference concentrations (< 1 μM), reduced cancer cell proliferation (by 10–20%) and VEGF production (by 37%), aggressiveness and metastatic potential of primary tumors through inducing mesenchymal-to-epithelial transition, increased antitumor immune response, OXPHOS and the TCA cycle. Part of these effects was due to activation of TGR5 by LCA. Early stage breast cancer patients, versus control women, had reduced serum LCA levels, reduced chenodeoxycholic acid to LCA ratio, and reduced abundance of the baiH (7α/β-hydroxysteroid dehydroxylase, the key enzyme in LCA generation) gene in fecal DNA, all suggesting reduced microbial generation of LCA in early breast cancer.

Original languageEnglish
JournalBiochimica et Biophysica Acta - Bioenergetics
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Lithocholic Acid
Cell proliferation
Metabolites
Cell Proliferation
Breast Neoplasms
Bile Acids and Salts
Hydroxysteroids
Chenodeoxycholic Acid
Epithelial-Mesenchymal Transition
Microbiota
Vascular Endothelial Growth Factor A
Tumors
Neoplasms
Genes
Chemical activation
Cells
Tissue
DNA
Enzymes
Serum

Keywords

  • Breast cancer
  • Endothelial-mesenchymal transition
  • Lithocholic acid
  • Microbiome
  • OXPHOS
  • TGR5

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness. / Mikó, Edit; Vida, András; Kovács, Tünde; Ujlaki, Gyula; Trencsényi, György; Márton, Judit; Sári, Zsanett; Kovács, Patrik; Boratkó, Anita; Hujber, Zoltán; Csonka, Tamás; Antal-Szalmás, Péter; Watanabe, Mitsuhiro; Gombos, Imre; Csoka, Balazs; Kiss, Borbála; Vígh, László; Szabó, Judit; Méhes, Gábor; Sebestyén, Anna; Goedert, James J.; Bai, Péter.

In: Biochimica et Biophysica Acta - Bioenergetics, 01.01.2018.

Research output: Contribution to journalArticle

Mikó, E, Vida, A, Kovács, T, Ujlaki, G, Trencsényi, G, Márton, J, Sári, Z, Kovács, P, Boratkó, A, Hujber, Z, Csonka, T, Antal-Szalmás, P, Watanabe, M, Gombos, I, Csoka, B, Kiss, B, Vígh, L, Szabó, J, Méhes, G, Sebestyén, A, Goedert, JJ & Bai, P 2018, 'Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness', Biochimica et Biophysica Acta - Bioenergetics. https://doi.org/10.1016/j.bbabio.2018.04.002
Mikó, Edit ; Vida, András ; Kovács, Tünde ; Ujlaki, Gyula ; Trencsényi, György ; Márton, Judit ; Sári, Zsanett ; Kovács, Patrik ; Boratkó, Anita ; Hujber, Zoltán ; Csonka, Tamás ; Antal-Szalmás, Péter ; Watanabe, Mitsuhiro ; Gombos, Imre ; Csoka, Balazs ; Kiss, Borbála ; Vígh, László ; Szabó, Judit ; Méhes, Gábor ; Sebestyén, Anna ; Goedert, James J. ; Bai, Péter. / Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness. In: Biochimica et Biophysica Acta - Bioenergetics. 2018.
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abstract = "Our study aimed at finding a mechanistic relationship between the gut microbiome and breast cancer. Breast cancer cells are not in direct contact with these microbes, but disease could be influenced by bacterial metabolites including secondary bile acids that are exclusively synthesized by the microbiome and known to enter the human circulation. In murine and bench experiments, a secondary bile acid, lithocholic acid (LCA) in concentrations corresponding to its tissue reference concentrations (< 1 μM), reduced cancer cell proliferation (by 10–20{\%}) and VEGF production (by 37{\%}), aggressiveness and metastatic potential of primary tumors through inducing mesenchymal-to-epithelial transition, increased antitumor immune response, OXPHOS and the TCA cycle. Part of these effects was due to activation of TGR5 by LCA. Early stage breast cancer patients, versus control women, had reduced serum LCA levels, reduced chenodeoxycholic acid to LCA ratio, and reduced abundance of the baiH (7α/β-hydroxysteroid dehydroxylase, the key enzyme in LCA generation) gene in fecal DNA, all suggesting reduced microbial generation of LCA in early breast cancer.",
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AU - Vida, András

AU - Kovács, Tünde

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AU - Trencsényi, György

AU - Márton, Judit

AU - Sári, Zsanett

AU - Kovács, Patrik

AU - Boratkó, Anita

AU - Hujber, Zoltán

AU - Csonka, Tamás

AU - Antal-Szalmás, Péter

AU - Watanabe, Mitsuhiro

AU - Gombos, Imre

AU - Csoka, Balazs

AU - Kiss, Borbála

AU - Vígh, László

AU - Szabó, Judit

AU - Méhes, Gábor

AU - Sebestyén, Anna

AU - Goedert, James J.

AU - Bai, Péter

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