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Lithocholic bile acid inhibits lipogenesis and induces apoptosis in breast cancer cells

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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.

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Acknowledgements

This study was funded by a grant from La Ligue Contre le Cancer de la Charente et de Loire Atlantique. Trang H. Luu was also funded by a research fellowship from the Vietnam Ministry of Education and Training and the Phu Tho Pharmacy College.

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Authors and Affiliations

  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

    Trang H. Luu, Jean-Marie Bard, Delphine Carbonnelle, Chloé Chaillou, Jean-Michel Huvelin, Christine Bobin-Dubigeon & Hassan Nazih

  2. ICO René Gauducheau, Unicancer, St Herblain, France

    Jean-Marie Bard & Christine Bobin-Dubigeon

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  1. Trang H. Luu
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Luu, T.H., Bard, JM., Carbonnelle, D. et al. Lithocholic bile acid inhibits lipogenesis and induces apoptosis in breast cancer cells. Cell Oncol. 41, 13–24 (2018). https://doi.org/10.1007/s13402-017-0353-5

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