Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jun 21;14(7):348.
doi: 10.3390/metabo14070348.

Bile Acids in Pancreatic Carcinogenesis

Bharti Sharma  1   2 , Kate Twelker  1   2 , Cecilia Nguyen  1   2 , Scott Ellis  1   2 , Navin D Bhatia  1   2 , Zachary Kuschner  1   2 , Andrew Agriantonis  2 , George Agriantonis  1   2 , Monique Arnold  2 , Jasmine Dave  1   2 , Juan Mestre  1   2 , Zahra Shafaee  1   2 , Shalini Arora  1   2 , Hima Ghanta  1   2 , Jennifer Whittington  1   2
Affiliations
Review

Bile Acids in Pancreatic Carcinogenesis

Bharti Sharma et al. Metabolites. .

Abstract

Pancreatic cancer (PC) is a dangerous digestive tract tumor that is becoming increasingly common and fatal. The most common form of PC is pancreatic ductal adenocarcinoma (PDAC). Bile acids (BAs) are closely linked to the growth and progression of PC. They can change the intestinal flora, increasing intestinal permeability and allowing gut microbes to enter the bloodstream, leading to chronic inflammation. High dietary lipids can increase BA secretion into the duodenum and fecal BA levels. BAs can cause genetic mutations, mitochondrial dysfunction, abnormal activation of intracellular trypsin, cytoskeletal damage, activation of NF-κB, acute pancreatitis, cell injury, and cell necrosis. They can act on different types of pancreatic cells and receptors, altering Ca2+ and iron levels, and related signals. Elevated levels of Ca2+ and iron are associated with cell necrosis and ferroptosis. Bile reflux into the pancreatic ducts can speed up the kinetics of epithelial cells, promoting the development of pancreatic intraductal papillary carcinoma. BAs can cause the enormous secretion of Glucagon-like peptide-1 (GLP-1), leading to the proliferation of pancreatic β-cells. Using Glucagon-like peptide-1 receptor agonist (GLP-1RA) increases the risk of pancreatitis and PC. Therefore, our objective was to explore various studies and thoroughly examine the role of BAs in PC.

Keywords: bile acids; genetic alteration; pancreatic cancer; tumorigenesis.

PubMed Disclaimer

Conflict of interest statement

The authors have no competing interests to declare.

Figures

Figure 1
Figure 1
Number of mortality cases associated with pancreatic cancer in the year 2022 (values are taken from Globocan, and the graph was designed by the authors) [10].
Figure 2
Figure 2
Number of cases showing mortality and incidence rates of pancreatic cancer (PC) across different continents in the year 2022 (values are taken from Globocan, and the graph was designed by authors) [10].
Figure 3
Figure 3
The 20 most frequently mutated genes in pancreatic cancer (PC). Names of genes are extracted from the NIH National Cancer Institute GDC data portal (explained in Table 1 of this paper) [47]. A string figure showing protein-to-protein association was created using STRING [48].
Figure 4
Figure 4
BA mechanisms of action in the progression of pancreatic cancer (Arrows facing upwards (in red) mean increase and arrows facing downwards (in red) mean decrease).
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Yadav D., Lowenfels A.B. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013;144:1252–1261. doi: 10.1053/j.gastro.2013.01.068. - DOI - PMC - PubMed
    1. Hezel A.F., Kimmelman A.C., Stanger B.Z., Bardeesy N., DePinho R.A. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 2006;20:1218–1249. doi: 10.1101/gad.1415606. - DOI - PubMed
    1. Williams D., Kenyon A., Adamson D. Basic Science in Obstetrics and Gynaecology. Elsevier; Amsterdam, The Netherlands: 2010. Physiology; pp. 173–230.
    1. Vertiprakhov V.G., Ovchinnikova N.V. The activity of trypsin in the pancreatic juice and blood of poultry increases simultaneously in the postprandial period. Front. Physiol. 2022;13:874664. doi: 10.3389/fphys.2022.874664. - DOI - PMC - PubMed
    1. Yamada T., Hasler W.L., Inadomi J.M. Structural Anomalies and Hereditary Diseases of the Pancreas. Lippincott Williams & Wilkins; Philadelphia, PA, USA: 2005. Gastroenterology, ed.

Grants and funding

There is no grant support or financial relationship for this manuscript.

LinkOut - more resources