Baicalein and baicalin in cancer therapy: Multifaceted mechanisms, preclinical evidence, and translational challenges

Abstract

Natural compounds with multitargeted actions are gaining prominence in oncology for their potential to complement and transcend the limitations of conventional therapies. Among them, baicalein and baicalin, two flavonoids primarily isolated from Scutellaria baicalensis, have attracted attention for their broad-spectrum anticancer properties. This review synthesizes current evidence from cellular systems, animal models, and early-phase clinical studies, exploring their pharmacological potential and translational relevance. Both molecules interfere with key hallmarks of cancer, including proliferation, survival, angiogenesis, metastasis, and immune evasion. Mechanistically, they modulate interconnected signaling cascades governing apoptosis, inflammation, and cell cycle control, and they enhance tumor sensitivity to chemotherapy and radiotherapy. In-vivo models consistently demonstrate tumor growth inhibition, while clinical data suggest a favorable safety profile, even at relatively high oral doses. However, their clinical translation remains hampered by limited solubility, poor oral bioavailability, and rapid metabolism, factors that continue to constrain their therapeutic window. Efforts to overcome these barriers through structural modification, encapsulation strategies, and advanced delivery systems are underway, yet few have advanced beyond preclinical validation. Despite these pharmacokinetic limitations, baicalein and baicalin remain compelling candidates for integrative oncological approaches. Their pleiotropic mechanisms, combined with low toxicity and synergistic behavior with standard therapies, position them as prototypes for a new generation of phytochemical-based anticancer agents. Continued work is needed to resolve formulation challenges and define precise molecular targets, but their trajectory reflects the growing scientific and clinical momentum around rationally designed natural compound therapeutics.

Keywords: Anticancer mechanisms; Baicalein; Baicalin; Bioavailability; Flavonoids; Oncology.