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Lithocholic Acid Induces Apoptosis Of Breast Cancer Cells MCF‐7 And Inhibits Lipogenesis
Author(s) -
Bard JeanMarie,
Luu Trang Huyen,
Carbonnelle Delphine,
Chailloux Chloé,
Huvelin JeanMichel,
BobinDubigeon Christine,
Nazih Hassan
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.790.1
Subject(s) - lipogenesis , deoxycholic acid , fatty acid synthase , lithocholic acid , chemistry , viability assay , apoptosis , biochemistry , lncap , cholic acid , bile acid , cancer cell , fatty acid , lipid metabolism , medicine , biology , endocrinology , cancer
Objectives Bile acids are products of cholesterol metabolism and their principal function is the solubilization of fats and liposoluble vitamins in the intestine. After their secretion into the intestine, primary bile acids are converted into secondary bile acids by intestinal bacteria. Two major secondary bile acids lithocholic acid (LCA) and deoxycholic acid (DCA) are produced from cholic acid and chenodeoxycholic acid, respectively. It has been reported that bile acids, particularly LCA have anti‐carcinogenic properties in several cancer cell models such as colon cancer, neuroblastoma cells, and prostate cancer. On the other hand, it is now recognized that the levels of the FASN enzyme (Fatty Acid Synthase) and lipogenesis are increased in the cancer cells. The aim of our study was to assess the effect of LCA on MCF‐7 breast cancer cells proliferation and apoptosis and to evaluate its influence on lipogenic enzymes and transcription factors related to lipogenesis. Material and Methods Anti‐proliferative properties of LCA were studied using the cell viability MTT assay and analysis of phospho‐Akt protein by FACS method. Apoptosis of MCF‐7 cells was examined by flow cytometer using Annexin‐FITC. QPCR and western blotting were used to study the expressions of genes and proteins involved in apoptosis (P53, Bcl‐2 and Bax) and in lipogenesis (LXR, SREBP‐1, FASN, ACC (Acetyl‐CoA Carboxylase) and SCD‐1 (Stearoyl‐coenzyme A desaturase‐1). Staining lipids by Oil Red O was used to study the lipid storage. Results LCA decreased the cell viability of MCF‐7 cells in a dose (25 to 200 microM)‐ and time (24 and 48h)‐ dependent manner. LCA also reduced Akt phosphorylation in a dose dependent manner (50% reduction at 100 microM, 24h). We also observed a decrease in the anti‐apoptotic protein Bcl‐2 and an increase in pro‐apoptotic protein p53, compared to untreated cells. Analyses by qPCR and Western blotting showed that LCA decreased at least by half the expression of LXR, SREBP‐1, FASN and ACC compared to untreated cells by LCA. Staining lipids by Oil Red O showed that MCF‐7 control cells contained abundant lipid droplets in comparison to LCA‐treated cells. Conclusion These data show that LCA has anti‐proliferative and pro‐apoptotic properties in MCF‐7 cells. Our study also suggests the potential capacity of LCA to induce apoptosis cancer cells by inhibiting the storage of lipids. Support or Funding Information Supported by Ligue contre le Cancer