Monemi Marzieh, Ahmed Hanan Hassan, Abdul Kareem Radhwan, Taher Waam Mohammed, Alwan Mariem, Jawad Mahmood Jasem, Hamad Atheer Khdyair, Moradi Samaneh
Department of Basic Science, Faculty of Pharmacy and Pharmaceutical Science, Tehran Medical Science, Islamic Azad University, Tehran, Iran.
College of Pharmacy, Alnoor University, Mosul, Iraq.
Int J Mol Cell Med. 2024;13(4):374-386. doi: 10.22088/IJMCM.BUMS.13.4.374.
It is expected that the amount of recently diagnosed colon cancer cases will increase to around 3.2 million yearly until 2040. Although early diagnostic procedures and management approaches have been improved, colorectal cancer (CRC) treatment remains challenging. There is an urgent need to discover new therapeutic agents to enhance therapeutic strategies. Ferroptosis is distinguished as a mode of regulated cell death considered by iron-dependent lipid peroxidation. Contemporary investigations suggest that induction of ferroptosis in CRC can effectively target neoplastic cells that are resistant to alternative forms of cell death. This review has summarized recent scientific work on the implications of ferroptosis in CRC treatment and highlights its underlying molecular and biological mechanisms. While investigating its therapeutic potential, it shows the importance of diverse modulators of ferroptosis, including the 7-membered solute carrier family 11 or xCT (SLC7A11), reactive oxygen species (ROS), glutathione (GSH), and iron in the context of CRC. Recent research has identified specific pathways and compounds that can induce ferroptosis in CRC, such as apatinib and elesclimol, which are involved in pivotal signaling cascades. Attenuation of proteins such as splicing factor, arginine/serine 9 (SFRS9), and Tp53-induced glycolysis and apoptosis regulator (TIGAR) may increase the sensitivity of CRC cells to ferroptosis, thus suggesting promising therapeutic avenues. Compounds including IMCA and β-elemene have shown efficacy in inducing ferroptosis while minimizing toxicity to normal tissues, thereby demonstrating their potential as therapeutic agents for CRC. Participating ferroptosis stimulator drugs with current treatment regimens, such as cetuximab and aspirin, may offer better treatment outcomes for CRC patients, especially those presenting resistance to conventional therapies.
预计到2040年，每年新诊断的结肠癌病例数量将增至约320万例。尽管早期诊断程序和治疗方法已有改进，但结直肠癌（CRC）的治疗仍然具有挑战性。迫切需要发现新的治疗药物以增强治疗策略。铁死亡是一种由铁依赖性脂质过氧化作用介导的程序性细胞死亡方式。当代研究表明，在结直肠癌中诱导铁死亡可有效靶向对其他形式细胞死亡具有抗性的肿瘤细胞。本综述总结了近期关于铁死亡在结直肠癌治疗中的意义的科学研究工作，并强调了其潜在的分子和生物学机制。在研究其治疗潜力时，本综述展示了铁死亡多种调节因子的重要性，包括在结直肠癌背景下的7成员溶质载体家族11或xCT（SLC7A11）、活性氧（ROS）、谷胱甘肽（GSH）和铁。最近的研究已经确定了可在结直肠癌中诱导铁死亡的特定途径和化合物，如阿帕替尼和艾乐替尼，它们参与关键信号级联反应。剪接因子精氨酸/丝氨酸9（SFRS9）和Tp53诱导的糖酵解和凋亡调节因子（TIGAR）等蛋白质的减少可能会增加结直肠癌细胞对铁死亡的敏感性，从而提示有前景的治疗途径。包括IMCA和β-榄香烯在内的化合物已显示出在诱导铁死亡的同时将对正常组织的毒性降至最低的效果，从而证明了它们作为结直肠癌治疗药物的潜力。将铁死亡刺激药物与当前治疗方案（如西妥昔单抗和阿司匹林）联合使用，可能会为结直肠癌患者带来更好的治疗效果，尤其是那些对传统疗法耐药的患者。
