Cancer is a multifactorial disease characterized by genetic mutations, deregulated signaling pathways, and immune evasion, all of which lead to uncontrolled cell proliferation and metastasis. Flavones, a prominent subclass of dietary flavonoids derived from medicinal plants, have emerged as promising anticancer agents due to their multitargeted pharmacological actions. Key flavones such as apigenin, luteolin, chrysin, baicalin, diosmetin, galangin, and nobiletin have been shown to demonstrate potent anticancer effects by inducing apoptosis, arresting the cell cycle, inhibiting angiogenesis, and modulating inflammatory and oxidative stress responses. These effects are primarily mediated through the modulation of crucial oncogenic pathways, including the PI3K/AKT/mTOR, JAK2/STAT3, Nrf2-HO-1, and ROS/Akt/mTOR pathways. The present review provides a comprehensive synthesis of preclinical and clinical studies, critically evaluating experimental models, study designs, and translational reliability. Special emphasis is given to methodological rigor, with consideration of xenografts, biomarker-based endpoints, and dosing strategies. The review also highlights major pharmacokinetic limitations, such as poor solubility, rapid metabolism, and low bioavailability, which impede clinical translation. To address these challenges, recent advances in nanoparticle-based delivery systems, structural analog development, and hybrid prodrug formulations are discussed. Additionally, the dual antioxidant and pro-oxidant roles of flavones are examined in the context of the tumor microenvironment and dose-dependent effects. The review further explores structurally related compounds, such as isocoumarins, that may offer complementary therapeutic benefits. Collectively, this analysis underscores the potential of flavones as integrative agents in cancer therapy and outlines future directions to enhance their clinical utility through precision-based and formulation-enhanced strategies.
Balkrishna et al. (Thu,) studied this question.