Research Progress of Bile Acids in Cancer

Bile acids (BAs), synthesized from cholesterol in the liver, are not only emulsifiers that promote lipid digestion and absorption but also serve as signal molecules to perform different biological functions.

Are bile acids foes or friends? This has been a controversial subject for a long time.

The knowledge of bile acids has been extended from promoting the absorption of lipids to key signalling molecules that maintain the body’s homeostasis. Especially in cancer, bile acids are giving more and more surprises in angiogenesis, cancer cell proliferation and death, tumour invasion and metastasis, inflammation and immune regulation, etc. Based on its nature and the wide variety of categories, bile acids play opposite roles in separate cancers, even the same cancer. This contradictory role endows bile acids with a mysterious content, however, the cytotoxic properties of bile acids has prompted researchers to explore ways to reduce cancer progression.

The effect of bile acids can be linked with cancer in several digestive (mainly oesophagus, stomach, liver, pancreas, biliary tract, colon) and extra-digestive organs (i.e. prostate, breast) through a complex series of mechanisms including direct oxidative stress with DNA damage, apoptosis, epigenetic factors regulating gene expression, reduced/increased expression of nuclear receptors and altered composition of gut microbiota, also acting as a common interface between environmental factors (including diet, lifestyle, exposure to toxics) and the molecular events promoting carcinogenesis.

Primary prevention strategies (i.e. changes in dietary habits and lifestyle, reduced exposure to environmental toxics) mainly able to modulate gut microbiota and the microbiome and the therapeutic use of hydrophilic bile acids to counterbalance the negative effects of the more bile acids might be, in the near future, part of useful tools for cancer prevention and management.

References:

Di Ciaula, A., Wang, D.Q.-H., Molina, E.M., Baccetto, R.L., Calamita, G., Palmieri, V.O., Portincasa, P. Bile acids and cancer: Direct and environmental-dependent effects Annals of Hepatology, Volume 16, November 2017