Targeting Cancer Hallmarks with Cirsium japonicum: Molecular Mechanisms and Therapeutic Potential

Cirsium japonicum is a medicinal plant traditionally used in East Asian medicine and contains multiple bioactive constituents with potential anticancer properties. This review critically evaluates the anticancer effects of C. japonicum and its associated constituents within the Hallmarks of Cancer framework. Evidence was classified as direct plant-specific evidence, constituent-based evidence, or contextual mechanistic evidence to distinguish findings obtained using botanical preparations from those generated using purified compounds derived from other sources. Direct studies of C. japonicum extracts, flavonoid fractions, phenylpropanoid glycosides, and C. japonicum var. maackii-mediated gold nanoparticles demonstrate antitumor, cytotoxic, antiangiogenic, immunomodulatory, and ferroptosis-associated activities, although target-level validation remains limited. Among its associated constituents, pectolinarigenin has the most developed mechanistic evidence, involving RRM2-CDK1, TOP2A, STAT3, and PI3K/AKT/mTOR signaling. Apigenin, luteolin, acacetin, linarin, cirsimaritin, and pectolinarin additionally influence regulated cell death, proliferative signaling, angiogenesis, metastasis, immune regulation, metabolic vulnerability, senescence, and therapy response. However, much of this evidence relies on pathway-associated changes rather than direct target engagement or genetic validation. Furthermore, the pharmacokinetics, systemic exposure, botanical standardization, tumor selectivity, and clinical relevance of these compounds remain insufficiently characterized. Future studies should prioritize standardized preparations, quantitative exposure analysis, functional target validation, clinically relevant models, and carefully designed combination strategies. Collectively, C. japonicum provides a promising multi-hallmark framework for anticancer investigation, but substantial translational evidence is still required before its therapeutic potential can be established.