Genistein in focus: pharmacological effects and immune pathway modulation in cancer

Cancer is a significant global health concern, responsible for mortality and morbidity of individuals. It is characterized by uncontrolled cellular growth, tumor formation, and potential metastasis. The immune system is pivotal in recognizing and eliminating cancerous cells, with immune cells such as T cells, B cells, natural killer cells (NK), and dendritic cells playing critical roles. Dysregulation of immune responses can contribute to cancer progression. Phytochemicals, bioactive compounds derived from plants, have gained attention for their potential roles in cancer prevention and therapy due to their antioxidant, anti-inflammatory, and immunomodulatory properties. Genistein, an isoflavone found in soy products, is of particular interest. In this study, genistein's mechanisms of action at the molecular and cellular levels in cancer were demonstrated, highlighting its impact on T and B lymphocytes, NK cells and dendritic cells. Genistein's ability to influence cytokine production, reducing levels of inflammatory cytokines such as TNF-α, IL-6, and IL-1β, is emphasized. Genistein modulates inflammatory response pathways like Toll-like receptors (TLRs), NF-κB, chemokines, and MAPK, inhibiting tumor growth, promoting apoptosis, and reducing metastasis. It shows promise in overcoming chemoresistance, particularly in ovarian and neuroblastoma cancers, by inhibiting autophagy. Genistein also affects T-cell execution markers, including granzyme B, TNF-α, and FAS ligand in cancer by influencing key proteins involved in immune response and apoptosis. Clinical trials have investigated genistein's therapeutic potential, revealing its promise in enhancing the efficacy of traditional cancer treatments while mitigating associated toxicities. Genistein helps overcome chemoresistance in various cancers by inhibiting autophagy and promoting apoptosis. It also enhances immunotherapy by boosting immune responses and modifying antigens, but careful dosing is needed when combined with anti-PD-1 treatments to avoid reducing effectiveness.