Kaempferol (KAE), a natural flavonoid, has emerged as a promising multi-target antineoplastic agent characterized by high efficacy and minimal systemic toxicity.Moving beyond fragmented descriptive summaries, this comprehensive review provides a highly integrated conceptual framework of KAE's anticancer mechanisms.Specifically, KAE orchestrates tumor eradication by enforcing cell cycle arrest across multiple phases and triggering a complex, interconnected network of programmed cell death.We highlight how reactive oxygen species and endoplasmic reticulum stress serve as central upstream nodes driving the mechanistic crosstalk among apoptosis, lethal autophagy, gasdermin E-mediated pyroptosis, and ferroptosis.Furthermore, KAE actively remodels the tumor microenvironment by inhibiting angiogenesis and repolarizing tumor-associated macrophages, thereby converting immunosuppressive "cold" tumors into immune-active "hot" tumors.Notably, this review introduces the emerging prebiotic-like crosstalk between KAE and the gut microbiome, providing a strong mechanistic rationale for its synergistic application with immune checkpoint inhibitors.As a potent chemosensitizer, KAE also overcomes multidrug resistance and mitigates chemotherapy-induced toxicities.Finally, we critically evaluate current translational bottlenecks-including the disparity between supraphysiological in vitro concentrations and clinical pharmacokinetics, the lack of robust in vivo validations, and the long-term biosafety of emerging nano-delivery systems.By addressing these critical limitations, this review offers strategic perspectives to bridge the gap from preliminary bench research to future precision oncological practice.
Cui et al. (Thu,) studied this question.
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