Unraveling the therapeutic potential of Calculus Bovis in liver cancer: A novel step for targeted cancer treatment

Abstract

Hepatocellular carcinoma is one of the leading causes of cancer-related deaths globally, and effective treatments are urgently needed. The present study aimed to investigate the inhibitory effect of Calculus Bovis (CB) on liver cancer and the underlying mechanisms. CB inhibited M2 tumor-associated macrophage polarization and modulated the Wnt/β-catenin signaling pathway, thereby suppressing the proliferation of liver cancer cells. The inhibitory effect on liver cancer growth was confirmed by both in vivo and in vitro experiments (detailed by Huang et al). The present study provides a theoretical basis for the application of CB for the treatment of liver cancer, providing new avenues for liver cancer treatment.

Key Words: Calculus Bovis; Liver cancer; M2 tumor-associated macrophage polarization; Wnt/β-catenin Pathway; Tumor microenvironment

Core Tip: Calculus Bovis (CB), a valuable herb in traditional Chinese medicine, has shown definite anti-liver cancer effects in vivo. Analyses of the composition of CB and the use of network pharmacology for target prediction revealed that CB has anti-liver cancer effects by affecting immune-related pathways in the tumor microenvironment. Transcriptome sequencing demonstrated that the regulation of the M2-type tumor-associated macrophage (TAM) polarization is responsible for the effects of CB. In vitro studies revealed that modulating the Wnt/β-catenin pathway is a crucial mechanism by which CB regulates M2 polarization of TAMs. The present study provides evidence for the development of liver cancer therapeutics.

TO THE EDITOR

We are delighted to read the high-quality article by Huang et al[1], published in the World Journal of Gastroenterology. This article delves into the antitumor mechanisms of Calculus Bovis (CB) in the context of liver cancer, offering novel perspectives for therapeutic approaches. By employing a multifaceted approach that includes UPLC-Q-TOF-MS analysis, network pharmacology, transcriptome profiling, and molecular docking, the authors provide a comprehensive account of how CB modulates the tumor microenvironment (TME), with a particular emphasis on the polarization of M2 tumor-associated macrophages (TAMs) and the Wnt/β-catenin signaling pathway. This modulation is crucial for inhibiting the polarization of M2 TAMs, thereby impeding tumor progression.

The World Journal of Gastroenterology recently published an engaging original article by Huang et al[1], which explored the mechanism underlying the antitumor effect of CB used in traditional Chinese medicine. In the TME, macrophages can polarize into an M1 or M2 phenotype, and M2-TAMs usually promote tumor growth and metastasis[2]. The study entitled, "Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/β-catenin pathway modulation to suppress liver cancer", demonstrated that CB exerts its effect by modulating the TME, especially via M2 TAM and the Wnt/β-catenin signaling pathway. CB inhibits M2-TAM polarization, thereby suppressing tumor growth. Moreover, the Wnt/β-catenin signaling pathway plays a crucial role in cell proliferation and differentiation, and it is often abnormal in liver cancer; CB regulates this pathway, thus inhibiting the proliferation of liver cancer cells and ultimately suppressing liver cancer growth.

Liver cancer has a high mortality rate and poor prognosis, representing a significant global health challenge[3,4]. Despite the progress made in surgical and pharmacological interventions, the search for novel treatment strategies that can effectively target disease progression remains crucial[5,6]. For a long time, traditional Chinese medicine has used the anti-inflammatory and immunomodulatory properties of CB to treat liver damage[7,8]. Some studies have shown that when combined with other traditional Chinese medicine components, CB exerts antitumor effects by synergistically affecting the metabolic pathways of cancer cells through multiple signaling pathways[9,10]. However, the comprehensive impact of CB on the TME of liver cancer, especially on TAMs, remains elusive[9]. In this context, the study by Huang et al[1] has emerged as a beacon of hope, demonstrating the potential of CB as a natural compound with antitumor properties.

Novelty

The novelty of the study by Huang et al[1] lies in its focus on M2-TAM polarization, a process that is of utmost importance for tumor growth and metastasis. Huang et al[1] initially demonstrated that CB suppresses tumor growth in an animal model. These researchers then performed a series of in vitro experiments, including cell culture, differentiation induction, CCK-8 assays, flow cytometry, cell scratch assays, Transwell assays, qRT-PCR, and Western blot analysis, to detect alterations in relevant cell indicators. Subsequently, these researchers applied network pharmacology to construct networks and conduct GO analysis, KEGG analysis, and molecular docking studies. Huang et al[1] also performed transcriptome analysis of gene changes. These investigations indicated that CB may inhibit M2-TAM polarization by modulating the Wnt/β-catenin pathway, thus providing a scientific rationale for its application in the treatment of liver cancer.

In addition to merely suppressing tumor growth, CB activates the apoptotic signaling pathway within liver cancer cells. This activation induces cancer cells to undergo apoptosis, thereby diminishing the survival capacity of tumor cells[9,10]. The present study focused on the regulatory function of CB with respect to M2 TAMs and the Wnt/β-catenin signaling pathway. The present study not only provides a scientific foundation for the traditional application of CB in cancer treatment but also highlights the path for the development of targeted therapies that harness the immunomodulatory effects of natural compounds. These findings imply that CB may serve as a valuable supplement in the battle against liver cancer, potentially supplementing existing therapies or offering alternatives to patients whose choices are restricted.

Compared with other investigations concerning liver cancer treatment, the research conducted by Huang and colleagues presents distinctive characteristics. Some traditional liver cancer treatment studies have focused predominantly on chemical drugs or surgical interventions[11,12], whereas the study by Huang et al[1] focused on the antitumor effect and mechanism of the natural drug CB. In contrast with other natural drug studies[13,14], the study by Huang et al[1] adopted a more systematic and comprehensive research approach by combining multiple techniques, such as UPLC-Q-TOF-MS analysis, network pharmacology, transcriptome analysis, and molecular docking, to comprehensively and profoundly explore the mechanism of action of CB. Nevertheless, the path toward clinical application is long and fraught with challenges. Future studies are needed to elucidate the precise mechanism by which the active constituents of CB regulate macrophage polarization and their synergistic effects in conjunction with current antitumor drugs. Additionally, the research findings must be verified in larger cohorts and translated into clinical trials to assess safety, efficacy, and the optimal dosage regimen. Overall, the study by Huang et al[1] offers novel ideas and directions for liver cancer treatment and complements other studies, jointly advancing the liver cancer treatment field.

CONCLUSION

In conclusion, the article by Huang et al[1] is a significant contribution to the fields of gastroenterology and oncology. The potential of traditional medicine in the context of modern cancer treatment is challenging. As we stand on the brink of new discoveries, the research community is encouraged to explore the depths of natural compounds, such as CB, and utilize their power to improve human health.