This cluster reflects a dominant research trajectory in hepatocellular carcinoma (HCC) biology: the convergence of natural/herbal bioactive compounds, network pharmacology, and mechanistic dissection of core oncogenic pathways—apoptosis, epithelial-mesenchymal transition (EMT), cell cycle arrest, and metastasis. Compounds such as Diosmetin, Ethanolic Extract of Centipeda Minima (ECM), Mentha, and Bazi Bushen exemplify a broader shift toward phytochemical and traditional-medicine-derived agents being systematically profiled through network pharmacology (identifying core targets like TNF, IL6, IL1B, and CASP3) and validated with standard functional assays (CCK-8, Transwell, colony formation, flow cytometry) in HepG2 and xenograft/nude mouse models. Mechanistically, these agents converge on the intrinsic apoptotic axis—upregulating pro-apoptotic effectors (Bax, CASP3) while suppressing Bcl2—and on EMT reversal, marked by E-cadherin restoration and N-cadherin/Vimentin downregulation, thereby impeding cell migration and invasion, two processes tightly linked to tumorigenesis and metastasis.
A second thematic layer centers on cellular stress and damage-sensing pathways as therapeutic levers against senescent or treatment-resistant tumor cells. Bazi Bushen exemplifies this by inducing mitochondrial damage and DNA leakage that activates cGAS-STING signaling in macrophages, enhancing immunosurveillance and triggering eradication of senescent liver cancer cells via host STING-dependent mechanisms—illustrating a growing interest in linking aging/senescence biology to innate immune activation for tumor repression. Similarly, ECM's ER stress/HMOX1/Fe2+/ROS pathway highlights oxidative and organelle-stress mechanisms (ferroptosis-adjacent) as inducers of G2/M cell cycle arrest and apoptosis, reinforcing a pattern where redox and organelle-damage pathways are being co-opted as anticancer mechanisms distinct from classical genotoxic chemotherapy.
Underlying these therapeutic narratives is a deeper molecular oncology thread involving epigenetic and metabolic regulation of malignancy: lncRNAs (HOTAIR) and m6A RNA modification machinery (METTL3/YTHDF1 stabilizing BFSP1 mRNA) that drive aerobic glycolysis, aggressive phenotypes, and poor prognosis, alongside metabolic enzymes like hexokinase linking glycolytic reprogramming to tumorigenesis. Collectively, this cluster portrays a research landscape bridging natural-product pharmacology, immune-stress signaling (cGAS-STING), epigenetic/RNA modification control, and classical hallmark pathways (apoptosis, EMT, invasion), all converging toward combination strategies that pair mechanistic biomarker discovery with translatable in vivo efficacy in HCC models.