Rana Juie Nahushkumar, Gul Kainat, Mumtaz Sohail
Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Department of Botany, Hazara University, Mansehra 21120, Pakistan.
Int J Mol Sci. 2025 Jul 30;26(15):7381. doi: 10.3390/ijms26157381.
Natural compounds, particularly flavonoids, have emerged as promising anticancer agents due to their various biological activities and no or negligible toxicity towards healthy tissues. Among these, isorhamnetin, a methylated flavonoid, has gained significant attention for its potential to target multiple cancer hallmarks. This review comprehensively explores the mechanisms by which isorhamnetin exerts its anticancer effects, including cell cycle regulation, apoptosis, suppression of metastasis and angiogenesis, and modulation of oxidative stress and inflammation. Notably, isorhamnetin arrests cancer cell proliferation by regulating cyclins, and CDKs induce apoptosis via caspase activation and mitochondrial dysfunction. It inhibits metastatic progression by downregulating MMPs, VEGF, and epithelial-mesenchymal transition (EMT) markers. Furthermore, its antioxidant and anti-inflammatory properties mitigate reactive oxygen species (ROS) and pro-inflammatory cytokines, restricting cancer progression and modulating tumor microenvironments. Combining isorhamnetin with other treatments was also discussed to overcome multidrug resistance. Importantly, this review integrates the recent literature (2022-2024) and highlights isorhamnetin's roles in modulating cancer-specific signaling pathways, immune evasion, tumor microenvironment dynamics, and combination therapies. We also discuss nanoformulation-based strategies that significantly enhance isorhamnetin's delivery and bioavailability. This positions isorhamnetin as a promising adjunct in modern oncology, capable of improving therapeutic outcomes when used alone or in synergy with conventional treatments. The future perspectives and potential research directions were also summarized. By consolidating current knowledge and identifying critical research gaps, this review positions Isorhamnetin as a potent and versatile candidate in modern oncology, offering a pathway toward safer and more effective cancer treatment strategies.
天然化合物,特别是黄酮类化合物,因其具有多种生物活性且对健康组织无毒性或毒性可忽略不计,已成为有前景的抗癌剂。其中,异鼠李素作为一种甲基化黄酮类化合物,因其靶向多种癌症特征的潜力而备受关注。本综述全面探讨了异鼠李素发挥抗癌作用的机制,包括细胞周期调控、凋亡、转移和血管生成抑制,以及氧化应激和炎症调节。值得注意的是,异鼠李素通过调节细胞周期蛋白和细胞周期蛋白依赖性激酶来阻止癌细胞增殖,通过半胱天冬酶激活和线粒体功能障碍诱导凋亡。它通过下调基质金属蛋白酶、血管内皮生长因子和上皮-间质转化(EMT)标志物来抑制转移进程。此外,其抗氧化和抗炎特性可减轻活性氧(ROS)和促炎细胞因子,限制癌症进展并调节肿瘤微环境。还讨论了将异鼠李素与其他治疗方法联合使用以克服多药耐药性。重要的是,本综述整合了最近的文献(2022 - 2024年),并强调了异鼠李素在调节癌症特异性信号通路、免疫逃逸、肿瘤微环境动态和联合治疗中的作用。我们还讨论了基于纳米制剂的策略,这些策略可显著提高异鼠李素的递送和生物利用度。这使异鼠李素成为现代肿瘤学中有前景的辅助药物,单独使用或与传统治疗协同使用时能够改善治疗效果。还总结了未来展望和潜在的研究方向。通过巩固现有知识并确定关键研究差距,本综述将异鼠李素定位为现代肿瘤学中一种有效且通用的候选药物,为更安全、更有效的癌症治疗策略提供了一条途径。
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