Colorectal cancer is the third most common malignancy worldwide and is often linked to obesity, a sedentary lifestyle, carbohydrate- and fat-rich diets and elevated fecal excretion of secondary bile acids. Accumulation of toxic bile acids triggers oxidative damage, mitochondrial dysfunction and tumor progression. Nuclear receptors are transcription factors crucially involved in the regulation of bile acid metabolism and detoxification, and their activation may confer protection from bile acid tumor-promoting activity. In this review, we explore the tangled relationships among bile acids, nuclear receptors and the intestinal epithelium, with particular emphasis on the role of the farnesoid X receptor in colorectal cancer prevention and on novel nuclear receptor-based approaches to expand the portfolio of chemotherapeutic agents
Bile acids and colon cancer: Solving the puzzle with nuclear receptors
PALASCIANO, Giuseppe;MOSCHETTA, ANTONIO
2011-01-01
Abstract
Colorectal cancer is the third most common malignancy worldwide and is often linked to obesity, a sedentary lifestyle, carbohydrate- and fat-rich diets and elevated fecal excretion of secondary bile acids. Accumulation of toxic bile acids triggers oxidative damage, mitochondrial dysfunction and tumor progression. Nuclear receptors are transcription factors crucially involved in the regulation of bile acid metabolism and detoxification, and their activation may confer protection from bile acid tumor-promoting activity. In this review, we explore the tangled relationships among bile acids, nuclear receptors and the intestinal epithelium, with particular emphasis on the role of the farnesoid X receptor in colorectal cancer prevention and on novel nuclear receptor-based approaches to expand the portfolio of chemotherapeutic agentsI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
