Calculus bovis hijacks the tumor microenvironment in liver cancer cells in a multifaceted approach: A falling row of dominoes
Year: 2024
Type: article
Abstract: Calculus bovis (C . bovis ) is widely used in traditional Chinese medicine due to its anti-tumor effects. C . bovis shifts liver cancer tumor microenvironment towards regression by hindering tumor-associated macrophages polarization. Huang et al have demonstrated in their study that C . bovis inhibits M2-tumour-associated macrophages (TAM) polarization by halting the Wnt/β-catenin pathway. The mechanism of action by which C . bovis exerts its anti-tumor effects is multifaceted and includes network pharmacology, transcriptomics and molecular docking. In vitro assays demonstrated that C . bovis -containing serum inhibited M2-TAMs polarization in human hepatocellular carcinomas cells. C . bovis was found to have 22 active components of which 11 were detected in the bloodstream. The anti-neoplastic activity of C . bovis lies in suppressing M2-TAM polarization by modulation of the Wnt/B-catenin pathway. In vitro and in vivo experiments have shown that C . bovis suppresses M2-TAM polarization and halts the Wnt signaling pathway. The inhibitory effect of C . bovis on M2-TAM was reversed by SKL2001, a Wnt agonist, which highlights C . bovis ’s selectivity and specificity. C . bovis inhibits M2-TAM polarization by modulating the Wnt/ β-catenin pathway, thus impeding liver cancer growth. Owing to the “cross-talk” between transforming growth factor-β (TGF-β) signaling pathways, this paper highlights the potential significance of C . bovis in controlling the tumor microenvironment not only through hindering the polarization of M2-TAMs via the Wnt signaling pathway, but also by downregulating TGF-β. Therefore, C . bovis serves as an igniter to fuel a cascade of signaling events that culminates in the regression of the tumor microenvironment by compromising oncogenesis and angiogenesis. TGF-β is also known for its pro-fibrotic properties. Therefore, C . bovis may play a pivotal role in treating liver fibrosis by downregulating TGF-β, thus hindering oncogenesis, angiogenesis and liver fibrosis. Hence, the “domino effect”.
Authors: Said G Farhat, Karam Karam
Institutions: Saint George Hospital, University of Balamand
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4404799731