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: Patrik Kov ács Tam ás Csonka T ünde Kovács Zsanett S ári Gyula Ujlaki Adrien Sipos Zsolt Kar ányi D óra Szeőcs Csaba Heged űs Karen Uray Laura Jank ó M áté Kiss Borb ála Kiss Damya Laoui L ászló Virág G ábor Méhes P éter Bai Edit Mik ó Tags: Article Source Type: research