Goleij Pouya, Tabari Mohammad Amin Khazeei, Khandan Mohanna, Poudineh Mohadeseh, Rezaee Aryan, Sadreddini Sarvin, Sanaye Pantea Majma, Khan Haroon, Larsen Danaé S, Daglia Maria
USERN Office, Kermanshah University of Medical Sciences, Kermanshah, 6715847141, Iran.
Department of Genetics, Faculty of Biology, Sana Institute of Higher Education, Sari, 4816118761, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):3557-3571. doi: 10.1007/s00210-024-03647-x. Epub 2024 Nov 27.
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.
癌症是一个重大的全球健康问题，关乎个人的死亡率和发病率。其特征为细胞不受控制地生长、肿瘤形成以及潜在的转移。免疫系统在识别和清除癌细胞方面起着关键作用，T细胞、B细胞、自然杀伤细胞（NK）和树突状细胞等免疫细胞发挥着至关重要的作用。免疫反应失调会促使癌症进展。植物化学物质是从植物中提取的生物活性化合物，因其抗氧化、抗炎和免疫调节特性，在癌症预防和治疗中的潜在作用受到关注。染料木黄酮是一种在豆制品中发现的异黄酮，尤其引人关注。在本研究中，展示了染料木黄酮在癌症中分子和细胞水平的作用机制，突出了其对T和B淋巴细胞、NK细胞及树突状细胞的影响。强调了染料木黄酮影响细胞因子产生、降低肿瘤坏死因子-α、白细胞介素-6和白细胞介素-1β等炎性细胞因子水平的能力。染料木黄酮调节Toll样受体（TLRs）、核因子-κB、趋化因子和丝裂原活化蛋白激酶等炎症反应途径，抑制肿瘤生长、促进细胞凋亡并减少转移。它在克服化学抗性方面显示出前景，特别是在卵巢癌和神经母细胞瘤中，通过抑制自噬来实现。染料木黄酮还通过影响参与免疫反应和细胞凋亡的关键蛋白，影响癌症中的T细胞执行标记，包括颗粒酶B、肿瘤坏死因子-α和FAS配体。临床试验研究了染料木黄酮的治疗潜力，揭示了其在提高传统癌症治疗疗效的同时减轻相关毒性方面的前景。染料木黄酮通过抑制自噬和促进细胞凋亡，有助于克服各种癌症中的化学抗性。它还通过增强免疫反应和修饰抗原增强免疫疗法，但与抗程序性死亡蛋白1（PD-1）治疗联合使用时需要谨慎给药，以避免降低疗效。
