Trang H Luu1, Jean-Marie Bard1,2, Delphine Carbonnelle1, Chloé Chaillou1, Jean-Michel Huvelin1, Christine Bobin-Dubigeon1,2, Hassan Nazih3. 1. Faculté de Pharmacie, EA 2160 MMS - Institut Universitaire Mer et Littoral FR3473 CNRS, Centre de Recherche en Nutrition Humaine Ouest (CRNH Ouest), ULB Université de Nantes, Nantes, France. 2. ICO René Gauducheau, Unicancer, St Herblain, France. 3. Faculté de Pharmacie, EA 2160 MMS - Institut Universitaire Mer et Littoral FR3473 CNRS, Centre de Recherche en Nutrition Humaine Ouest (CRNH Ouest), ULB Université de Nantes, Nantes, France. el-hassane.nazih@univ-nantes.fr.
Abstract
BACKGROUND: It has amply been documented that mammary tumor cells may exhibit an increased lipogenesis. Biliary acids are currently recognized as signaling molecules in the intestine, in addition to their classical roles in the digestion and absorption of lipids. The aim of our study was to evaluate the impact of lithocholic acid (LCA) on the lipogenesis of breast cancer cells. The putative cytotoxic effects of LCA on these cells were also examined. METHODS: The effects of LCA on breast cancer-derived MCF-7 and MDA-MB-231 cells were studied using MTT viability assays, Annexin-FITC and Akt phosphorylation assays to evaluate anti-proliferative and pro-apoptotic properties, qRT-PCR and Western blotting assays to assess the expression of the bile acid receptor TGR5 and the estrogen receptor ERα, and genes and proteins involved in apoptosis (Bax, Bcl-2, p53) and lipogenesis (SREBP-1c, FASN, ACACA). Intracellular lipid droplets were visualized using Oil Red O staining. RESULTS: We found that LCA induces TGR5 expression and exhibits anti-proliferative and pro-apoptotic effects in MCF-7 and MDA-MB-231 cells. Also, an increase in pro-apoptotic p53 protein expression and a decrease in anti-apoptotic Bcl-2 protein expression were observed after LCA treatment of MCF-7 cells. In addition, we found that LCA reduced Akt phosphorylation in MCF-7 cells, but not in MDA-MB-231 cells. We also noted that LCA reduced the expression of SREBP-1c, FASN and ACACA in both breast cancer-derived cell lines and that cells treated with LCA contained low numbers of lipid droplets compared to untreated control cells. Finally, a decrease in ERα expression was observed in MCF-7 cells treated with LCA. CONCLUSIONS: Our data suggest a potential therapeutic role of lithocholic acid in breast cancer cells through a reversion of lipid metabolism deregulation.
BACKGROUND: It has amply been documented that mammary tumor cells may exhibit an increased lipogenesis. Biliary acids are currently recognized as signaling molecules in the intestine, in addition to their classical roles in the digestion and absorption of lipids. The aim of our study was to evaluate the impact of lithocholic acid (LCA) on the lipogenesis of breast cancer cells. The putative cytotoxic effects of LCA on these cells were also examined. METHODS: The effects of LCA on breast cancer-derived MCF-7 and MDA-MB-231 cells were studied using MTT viability assays, Annexin-FITC and Akt phosphorylation assays to evaluate anti-proliferative and pro-apoptotic properties, qRT-PCR and Western blotting assays to assess the expression of the bile acid receptor TGR5 and the estrogen receptor ERα, and genes and proteins involved in apoptosis (Bax, Bcl-2, p53) and lipogenesis (SREBP-1c, FASN, ACACA). Intracellular lipid droplets were visualized using Oil Red O staining. RESULTS: We found that LCA induces TGR5 expression and exhibits anti-proliferative and pro-apoptotic effects in MCF-7 and MDA-MB-231 cells. Also, an increase in pro-apoptotic p53 protein expression and a decrease in anti-apoptotic Bcl-2 protein expression were observed after LCA treatment of MCF-7 cells. In addition, we found that LCA reduced Akt phosphorylation in MCF-7 cells, but not in MDA-MB-231 cells. We also noted that LCA reduced the expression of SREBP-1c, FASN and ACACA in both breast cancer-derived cell lines and that cells treated with LCA contained low numbers of lipid droplets compared to untreated control cells. Finally, a decrease in ERα expression was observed in MCF-7 cells treated with LCA. CONCLUSIONS: Our data suggest a potential therapeutic role of lithocholic acid in breast cancer cells through a reversion of lipid metabolism deregulation.
Entities:
Keywords:
Breast cancer; Gut microbiota; Lipogenesis; Lithocholic acid; MCF-7 cells; MDA-MB-231 cells; TGR5 activation
Authors: Simon M Vogel; Matthias R Bauer; Andreas C Joerger; Rainer Wilcken; Tobias Brandt; Dmitry B Veprintsev; Trevor J Rutherford; Alan R Fersht; Frank M Boeckler Journal: Proc Natl Acad Sci U S A Date: 2012-10-03 Impact factor: 11.205
Authors: Arezoo Astanehe; David Arenillas; Wyeth W Wasserman; Peter C K Leung; Sandra E Dunn; Barry R Davies; Gordon B Mills; Nelly Auersperg Journal: J Cell Sci Date: 2008-02-12 Impact factor: 5.285
Authors: B S Tan; K H Tiong; H L Choo; F Fei-Lei Chung; L-W Hii; S H Tan; I K S Yap; S Pani; N T W Khor; S F Wong; R Rosli; S-K Cheong; C-O Leong Journal: Cell Death Dis Date: 2015-07-16 Impact factor: 8.469
Authors: Anthony Arlia-Ciommo; Anna Leonov; Karamat Mohammad; Adam Beach; Vincent R Richard; Simon D Bourque; Michelle T Burstein; Alexander A Goldberg; Pavlo Kyryakov; Alejandra Gomez-Perez; Olivia Koupaki; Vladimir I Titorenko Journal: Oncotarget Date: 2018-10-09
Authors: Advait Shetty; Prashanth K B Nagesh; Saini Setua; Bilal B Hafeez; Meena Jaggi; Murali M Yallapu; Subhash C Chauhan Journal: ACS Omega Date: 2020-04-13