Concentration-dependent effects of sodium cholate and deoxycholate bile salts on breast cancer cells proliferation and survival

Bile acids (BAs) are bioactive molecules that have potential therapeutic interest and their derived salts are used in several pharmaceutical systems. BAs have been associated with tumorigenesis of several tissues including the mammary tissue. Therefore, it is crucial to characterize their effects on...

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Bibliographic Details
Published in:	Molecular biology reports Vol. 47; no. 5; pp. 3521 - 3539
Main Authors:	Gándola, Yamila B., Fontana, Camila, Bojorge, Mariana A., Luschnat, Tania T., Moretton, Marcela A., Chiapetta, Diego A., Verstraeten, Sandra V., González, Lorena
Format:	Journal Article
Language:	English
Published:	Dordrecht Springer Netherlands 01-05-2020 Springer Nature B.V
Subjects:	AKT protein Animal Anatomy Animal Biochemistry Anisotropy Apoptosis Bile Bile acids Bile Acids and Salts - metabolism Bile Acids and Salts - pharmacology Bile salts Biomedical and Life Sciences Breast cancer Breast Neoplasms - metabolism Cell activation Cell adhesion & migration Cell Line, Tumor Cell membranes Cell migration Cell proliferation Cell Proliferation - drug effects Cell Survival - drug effects Cell viability Cyclin D1 Cytology Cytotoxicity Deoxycholic Acid - metabolism Deoxycholic Acid - pharmacology Fluidity Histology Humans Life Sciences Light scattering Membrane fluidity Microscopy Morphology Original Article Phosphorylation Salts Sodium Sodium cholate Sodium Cholate - metabolism Sodium Cholate - pharmacology Sodium deoxycholate Transmission electron microscopy Tumor cell lines Tumorigenesis Receptors Plasma membrane Protein phosphorylation Bile acids and salts Breast cancer cells Cell signaling Apoptosis Cancer
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Summary:	Bile acids (BAs) are bioactive molecules that have potential therapeutic interest and their derived salts are used in several pharmaceutical systems. BAs have been associated with tumorigenesis of several tissues including the mammary tissue. Therefore, it is crucial to characterize their effects on cancer cells. The objective of this work was to analyse the molecular and cellular effects of the bile salts sodium cholate and sodium deoxycholate on epithelial breast cancer cell lines. Bile salts (BSs) effects over breast cancer cells viability and proliferation were assessed by MTS and BrdU assays, respectively. Activation of cell signaling mediators was determined by immunobloting. Microscopy was used to analyze cell migration, and cellular and nuclear morphology. Interference of membrane fluidity was studied by generalized polarization and fluorescence anisotropy. BSs preparations were characterized by transmission electron microscopy and dynamic light scattering. Sodium cholate and sodium deoxycholate had dual effects on cell viability, increasing it at the lower concentrations assessed and decreasing it at the highest ones. The increase of cell viability was associated with the promotion of AKT phosphorylation and cyclin D1 expression. High concentrations of bile salts induced apoptosis as well as sustained activation of p38 and AKT. In addition, they affected cell membrane fluidity but not significant effects on cell migration were observed. In conclusion, bile salts have concentration-dependent effects on breast cancer cells, promoting cell proliferation at physiological levels and being cytotoxic at supraphysiological ones. Their effects were associated with the activation of kinases involved in cell signalling.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0301-4851 1573-4978
DOI:	10.1007/s11033-020-05442-2