Cancers, Vol. 11, Pages 1255: Lithocholic Acid, a Metabolite of the Microbiome, Increases Oxidative Stress in Breast Cancer

Cancers, Vol. 11, Pages 1255: Lithocholic Acid, a Metabolite of the Microbiome, Increases Oxidative Stress in Breast Cancer Cancers doi: 10.3390/cancers11091255 Authors: Patrik Kovács Tamás Csonka Tünde Kovács Zsanett Sári Gyula Ujlaki Adrien Sipos Zsolt Karányi Dóra Szeőcs Csaba Hegedűs Karen Uray Laura Jankó Máté Kiss Borbála Kiss Damya Laoui László Virág Gábor Méhes Péter Bai Edit Mikó In breast cancer patients, the diversity of the microbiome decreases, coinciding with decreased production of cytostatic bacterial metabolites like lithocholic acid (LCA). We hypothesized that LCA can modulate oxidative stress to exert cytostatic effects in breast cancer cells. Treatment of breast cancer cells with LCA decreased nuclear factor-2 (NRF2) expression and increased Kelch-like ECH associating protein 1 (KEAP1) expression via activation of Takeda G-protein coupled receptor (TGR5) and constitutive androstane receptor (CAR). Altered NRF2 and KEAP1 expression subsequently led to decreased expression of glutathione peroxidase 3 (GPX3), an antioxidant enzyme, and increased expression of inducible nitric oxide synthase (iNOS). The imbalance between the pro- and antioxidant enzymes increased cytostatic effects via increased levels of lipid and protein oxidation. These effects were reversed by the pharmacological induction of NRF2 with RA839, tBHQ, or by thiol antioxidants. The expression of key components of the LCA-elicited cy...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research