MO_III_L: Molecular Sciences III. Lectures
University of Debrecen Faculty of Medicine Department of Medical Chemistry, Debrecen
The effects of lithocolic acid on oxidative stress in breast cancer
The human body is colonized by various symbiotic, commensal, and pathogenic microorganisms, which live on the surface of the skin and in the cavities of the body. The collective genome of the microorganisms is called microbiome. The pathogenic dysbiosis of the microbiome is linked with numerous pathophysiological processes such as certain tumor formation processes. The diversity of the microbiome decreases in breast cancer patients, coinciding with decreased production of lithocolic acid (LCA). LCA is a secondary bile acid that is produced from a primary bile acid, chenodeoxycholic acid by the microbiome of the intestines.
Our aim was to explore how the LCA modulate oxidative and nitrosative stress in breast cancer cells.
For the experiments we use SulforhodamineB assay, RT-QPCR, Western blot and TBARS assay.
The LCA, a bacterial metabolite, increases the level of the oxidative and nitrosative stress by creating an imbalance between pro- and antioxidant system in breast cancer cells. The expression of nuclear factor-2 (NRF2) is reduced, and the expression of Kelch-like ECH associating protein 1 (KEAP1) increased after treatment with LCA. Altered NRF2 and KEAP1 led to decreased expression of glutathione peroxidase 3 (GPX3), an antioxidant enzyme, and increased the expression of inducible nitric oxide synthase (iNOS). The level of protein and lipid peroxidation increased after the LCA treatment. The levels of thiobarbituric acid reactive species and the level of 4-hydroxynonenal increased after treatment with LCA. The effects of LCA abolished upon genetic and phermacological inhibition of Takeda G-protein coupled receptor and the constitutive androstane receptor.
We showed that the cytostatic effects of LCA depends on the downregulation of NRF2 expression and the induction of oxidative and nitrosative stress. We also showed that the LCA elicits these effects via activation of Takeda G-protein coupled receptor and constitutive androstane receptor.
The work is supported by Hungarian National Research, Development and Innovation Office (ÚNKP-20-3-I-DE-301).
University: University of Deberecen, Doctoral School of Molecular Medicine
Supervisor: Kapitányné Dr. Mikó Edit (email@example.com)
Debrecen University Faculty of Medicine, Doctoral School of Molecular Medicine