Calculus bovis in hepatocellular carcinoma: Tumor molecular basis, Wnt/β-catenin pathway role, and protective mechanism

Abstract

In this editorial, we comment on the recent article by Huang et al. The editorial focuses specifically on the molecular mechanisms of hepatocellular carcinoma (HCC), mechanism of Wnt/β-catenin pathway in HCC, and protective mechanism of Calculus bovis (CB) in HCC. Liver cancer is the fourth most common cause of cancer-related deaths globally. The most prevalent kind of primary liver cancer, HCC, is typically brought on by long-term viral infections (hepatitis B and C), non-alcoholic steatohepatitis, excessive alcohol consumption, and other conditions that can cause the liver to become chronically inflamed and cirrhotic. CB is a well-known traditional remedy in China and Japan and has been used extensively to treat a variety of diseases, such as high fever, convulsions, and stroke. Disturbances in lipid metabolism, cholesterol metabolism, bile acid metabolism, alcohol metabolism, and xenobiotic detoxification lead to fatty liver disease and liver cirrhosis. Succinate, which is a tricarboxylic acid cycle intermediate, is vital to energy production and mitochondrial metabolism. It is also thought to be a signaling molecule in metabolism and in the development and spread of liver malignancies. The Wnt/β-catenin pathway is made up of a group of proteins that are essential for both adult tissue homeostasis and embryonic development. Cancer is frequently caused by the dysregulation of the Wnt/β-catenin signaling pathway. In HCC liver carcinogenesis, Wnt/β-catenin signaling is activated by the expression of downstream target genes. Communication between the liver and the gut exists via the portal vein, biliary tract, and systemic circulation. This "gut-liver axis" controls intestinal physiology. One of the main factors contributing to the development, progression, and treatment resistance of HCC is the abnormal activation of the Wnt/β-Catenin signaling pathway. Therefore, understanding this pathway is essential to treating HCC. Eleven ingredients of CB, particularly oleanolic acid, ergosterol, and ursolic acid, have anti-primary liver cancer properties. Additionally, CB is important in the treatment of primary liver cancer through pathways linked to immune system function and apoptosis. CB also inhibits the proliferation of cancer stem cells and tumor cells and controls the tumor microenvironment. In the future, clinicians may be able to recommend one of many potential new drugs from CB ingredients to treat HCC expression, development, and progress.

Keywords: Hepatocellular carcinoma; MicroRNAs; Wnt/β-catenin pathway; Calculus bovis; Apoptosis

Core Tip: Disturbances in lipid metabolism, cholesterol metabolism, bile acid metabolism, alcohol metabolism, and xenobiotic detoxification lead to fatty liver disease and liver cirrhosis. Dysregulation of the Wnt/β-catenin signaling pathway occurs due to liver cancer. Oleanolic acid, ergosterol, and ursolic acid are Calculus bovis (CB) ingredients with anti-primary liver cancer properties. Additionally, CB is important in the treatment of primary liver cancer through the Wnt/β-catenin pathway linked to immunity and apoptosis.