Search

Traditional Chinese medicine (TCM) is considered to be one of the most comprehensive and influential form of traditional medicine. It plays an important role in clinical treatment and adjuvant therapy for cancer. However, the complex composition of TCM presents challenges to the comprehensive and systematic understanding of its antitumor mechanisms, which hinders further development of TCM with antitumor effects. Omics technologies can immensely help in elucidating the mechanism of action of drugs. They utilize high-throughput sequencing and detection techniques to provide deeper insights into biological systems, revealing the intricate mechanisms through which TCM combats tumors. Multi-omics approaches can be used to elucidate the interrelationships among different omics layers by integrating data from various omics disciplines. By analyzing a large amount of data, these approaches further unravel the complex network of mechanisms underlying the antitumor effects of TCM and explain the mutual regulations across different molecular levels. In this study, we presented a comprehensive overview of the recent progress in single-omics and multi-omics research focused on elucidating the mechanisms underlying the antitumor effects of TCM. We discussed the significance of omics technologies in advancing research on the antitumor properties of TCM and also provided novel research perspectives and methodologies for further advancing this research field. [ABSTRACT FROM AUTHOR]

Background: Usenamine A, a novel natural compound initially isolated from the lichen Usnea longissima, has exhibited promising efficacy against hepatoma in prior investigation. Nevertheless, the underlying mechanisms responsible for its antihepatoma effects remain unclear. Furthermore, the role of the AKT/mechanistic target of the rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3)/inhibitor of differentiation/DNA binding 1 (ID1) signaling axis in hepatocellular carcinoma (HCC), and the potential anti-HCC effects of drugs targeting this pathway are not well understood. Methods: CCK-8 assay was used to investigate the effects of usenamine A on the proliferation of human HCC cells. Moreover, the effects of usenamine A on the invasion ability of human HCC cells were evaluated by transwell assay. In addition, expression profiling analysis, quantitative real-time PCR, immunoblotting, immunohistochemistry (IHC) analysis, RNAi, immunoprecipitation, and chromatin immunoprecipitation (ChIP) assay were used to explore the effects of usenamine A on the newly identified AKT/mTOR/STAT3/ID1 signaling axis in human HCC cells. Results: Usenamine A inhibited the proliferation and invasion of human HCC cell lines (HepG2 and SK-HEP-1). Through the analysis of gene expression profiling, we identified that usenamine A suppressed the expression of ID1 in human HCC cells. Furthermore, immunoprecipitation experiments revealed that usenamine A facilitated the degradation of the ID1 protein via the ubiquitin–proteasome pathway. Moreover, usenamine A inhibited the activity of STAT3 in human HCC cells. ChIP analysis demonstrated that STAT3 positively regulated ID1 expression at the transcriptional level in human HCC cells. The STAT3/ID1 axis played a role in mediating the anti-proliferative and anti-invasive impacts of usenamine A on human HCC cells. Additionally, usenamine A suppressed the STAT3/ID1 axis through AKT/mTOR signaling in human HCC cells. Conclusion: Usenamine A displayed robust anti-HCC potential, partly attributed to its capacity to downregulate the AKT/mTOR/STAT3/ID1 signaling pathway and promote ubiquitin–proteasome-mediated ID1 degradation. Usenamine A has the potential to be developed as a therapeutic agent for HCC cases characterized by abnormal AKT/mTOR/STAT3/ID1 signaling, and targeting the AKT/mTOR/STAT3 signaling pathway may be a viable option for treating patients with HCC exhibiting elevated ID1 expression. [ABSTRACT FROM AUTHOR]

Ferroptosis is a non-apoptotic form of regulated cell death characterized by iron-dependent lipid peroxidation. It can be triggered by various mechanisms, including the glutathione peroxidase 4 (GPX4)-glutathione (GSH) axis, iron metabolism, lipid metabolism, the GTP cyclohydrolase 1 (GCH1)-tetrahydrobiopterin (BH4) pathway, and the ferroptosis suppressor protein 1 (FSP1)-coenzyme Q10 axis. The redox balance is disrupted when ferroptosis occurs in cells, which is fatal to cancer cells. Additionally, some tumor-associated genes are involved in ferroptosis. Hence, targeting ferroptosis might be an effective strategy for treating cancer. Several small-molecule compounds exhibit anti-tumor effects through ferroptosis, including sorafenib and altretamine, which induce ferroptosis by inhibiting System-Xc and GPX4 respectively, but many problems, such as poor druggability, still exist. Some studies have shown that many traditional Chinese medicine (TCM) induce ferroptosis by inhibiting GPX4, solute carrier family 7 member 11 (SLC7A11), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), or by increasing the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4), transferrin (TF), and transferrin receptor 1 (TFR1). These changes can lead to the lysosomal degradation of ferritin, accumulation of iron, lipid peroxidation and the production of reactive oxygen species (ROS), which in turn can promote anti-tumor activities or synergistic effects with chemotherapeutic drugs. In this study, we elucidated the underlying mechanisms of ferroptosis, and the anti-tumor pharmacology of TCM targeting ferroptosis including prescriptions, Chinese herbs, extracts, and natural compounds. Our findings might act as valuable reference for research on anti-tumor drugs targeting ferroptosis, especially those drugs developed from TCM. [ABSTRACT FROM AUTHOR]

The gut microbiota, known as the "forgotten organ" and "human second genome," comprises a complex microecosystem. It significantly influences the development of various tumors, including colorectal, liver, stomach, breast, and lung cancers, through both direct and indirect mechanisms. These mechanisms include the "gut-liver" axis, the "lung-intestine" axis, and interactions with the immune system. The intestinal flora exhibits dual roles in cancer, both promoting and suppressing its progression. Traditional Chinese medicine (TCM) can alter cancer progression by regulating the intestinal flora. It modifies the intestinal flora's composition and structure, along with the levels of endogenous metabolites, thus affecting the intestinal barrier, immune system, and overall body metabolism. These actions contribute to TCM's significant antitumor effects. Moreover, the gut microbiota metabolizes TCM components, enhancing their antitumor properties. Therefore, exploring the interaction between TCM and the intestinal flora offers a novel perspective in understanding TCM's antitumor mechanisms. This paper succinctly reviews the association between gut flora and the development of tumors, including colorectal, liver, gastric, breast, and lung cancers. It further examines current research on the interaction between TCM and intestinal flora, with a focus on its antitumor efficacy. It identifies limitations in existing studies and suggests recommendations, providing insights into antitumor drug research and exploring TCM's antitumor effectiveness. Additionally, this paper aims to guide future research on TCM and the gut microbiota in antitumor studies. [Display omitted] • Numerous tumor mechanisms are intricately connected with gut microbiota. • TCM affects gut microbiota to exert antitumor effects through diverse mechanisms. • Gut microbiota plays a role in the conversion of TCM to enhance antitumor efficacy. • Overcoming the challenge of interaction between TCM and gut microbiota is essential. [ABSTRACT FROM AUTHOR]