Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland.
Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Int J Mol Sci. 2024 Jul 15;25(14):7725. doi: 10.3390/ijms25147725.
Nature provides us with a rich source of compounds with a wide range of applications, including the creation of innovative drugs. Despite advancements in chemically synthesized therapeutics, natural compounds are increasingly significant, especially in cancer treatment, a leading cause of death globally. One promising approach involves the use of natural inhibitors of checkpoint kinase 2 (Chk2), a critical regulator of DNA repair, cell cycle arrest, and apoptosis. Chk2's activation in response to DNA damage can lead to apoptosis or DNA repair, influencing glycolysis and mitochondrial function. In cancer therapy, inhibiting Chk2 can disrupt DNA repair and cell cycle progression, promoting cancer cell death and enhancing the efficacy of radiotherapy and chemotherapy. Additionally, Chk2 inhibitors can safeguard non-cancerous cells during these treatments by inhibiting p53-dependent apoptosis. Beyond oncology, Chk2 inhibition shows potential in treating hepatitis C virus (HCV) infections, as the virus relies on Chk2 for RNA replication in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), in which DNA damage plays a crucial role. Plant-derived Chk2 inhibitors, such as artemetin, rhamnetin, and curcumin, offer a promising future for treating various diseases with potentially milder side effects and broader metabolic impacts compared to conventional therapies. The review aims to underscore the immense potential of natural Chk2 inhibitors in various therapeutic contexts, particularly in oncology and the treatment of other diseases involving DNA damage and repair mechanisms. These natural Chk2 inhibitors hold significant promise for revolutionizing the landscape of cancer treatment and other diseases. Further research into these compounds could lead to the development of innovative therapies that offer hope for the future with fewer side effects and enhanced efficacy.
自然界为我们提供了丰富的化合物资源,这些化合物具有广泛的应用,包括创新药物的研发。尽管化学合成疗法取得了进展,但天然化合物的重要性日益凸显,尤其是在癌症治疗方面,癌症是全球主要的死亡原因之一。一种有前途的方法是利用天然的细胞周期检查点激酶 2(Chk2)抑制剂,Chk2 是 DNA 修复、细胞周期阻滞和细胞凋亡的关键调节因子。Chk2 在应对 DNA 损伤时的激活会导致细胞凋亡或 DNA 修复,从而影响糖酵解和线粒体功能。在癌症治疗中,抑制 Chk2 可以破坏 DNA 修复和细胞周期进程,促进癌细胞死亡,并增强放疗和化疗的疗效。此外,Chk2 抑制剂可以通过抑制 p53 依赖性细胞凋亡来保护非癌细胞。除了肿瘤学,Chk2 抑制在治疗丙型肝炎病毒(HCV)感染方面也显示出潜力,因为该病毒依赖 Chk2 进行 RNA 复制。在神经退行性疾病(如肌萎缩侧索硬化症(ALS))中,Chk2 抑制剂在其中发挥作用,因为 DNA 损伤在其中发挥关键作用。来自植物的 Chk2 抑制剂,如青蒿素、鼠李素和姜黄素,为治疗各种疾病提供了有前途的未来,与传统疗法相比,这些抑制剂具有潜在的更温和的副作用和更广泛的代谢影响。本文综述强调了天然 Chk2 抑制剂在各种治疗环境中的巨大潜力,特别是在肿瘤学和涉及 DNA 损伤和修复机制的其他疾病的治疗中。这些天然 Chk2 抑制剂为癌症治疗和其他疾病的治疗带来了革命性的变化,具有很大的潜力。对这些化合物的进一步研究可能会导致开发出更具创新性的治疗方法,为未来带来希望,副作用更小,疗效更高。