Vidanapathirana Gihani, Islam Md Sajedul, Gamage Sujani, Lam Alfred K, Gopalan Vinod
School of Medicine and Dentistry, Griffith University, Gold Coast Campus, Southport, Queensland, Australia.
Department of Medical Laboratory Science, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka.
Cancer Med. 2025 Jul;14(13):e71019. doi: 10.1002/cam4.71019.
Despite significant therapeutic advancements in recent decades, colorectal cancer (CRC) continues to exhibit high rates of mortality and morbidity. Chemoresistance and cancer recurrence remain substantial challenges, underscoring the need for novel treatment approaches. Iron chelation therapy has gained profound interest over the years as a potential cancer treatment, leveraging the increased iron demand by tumors. This review evaluates the effects of iron chelation therapy on CRC progression and the underlying mechanisms.
A comprehensive review of in vivo and in vitro studies was conducted to assess the effectiveness of iron chelation therapy in CRC. The literature search covered PubMed, Scopus, Medline (via Web of Science), and EMBASE between January 1995 and March 2024.
Several in vitro and in vivo studies have investigated the impact of iron chelators, such as deferoxamine, deferasirox, thiosemicarbazone-based chelators, quilamine-based chelators, and other novel compounds on CRC. Natural plant extracts with iron-chelating properties have also been explored as potential treatments. Most studies indicate that iron chelation can inhibit the proliferation of colon cancer cells, though some studies suggest cancer-promoting effects. Mechanistically, iron chelation affects several hallmarks of CRC by modulating histone methylation, upregulating NDRG1, and influencing the Wnt/β-catenin and p53 signaling pathways. However, certain iron chelators may inhibit TRAIL-mediated apoptosis and activate the hypoxia-inducible factor (HIF), potentially accelerating CRC progression.
Future exploration of iron chelation therapy in CRC should focus on extensive in vitro, in vivo, and clinical studies to elucidate the precise mechanisms involved. A deeper understanding of the genetic and cellular alterations induced by iron chelation will enhance the development of effective therapeutic strategies for CRC.
尽管近几十年来在治疗方面取得了重大进展，但结直肠癌（CRC）的死亡率和发病率仍然很高。化疗耐药性和癌症复发仍然是重大挑战，这突出了对新型治疗方法的需求。多年来，铁螯合疗法作为一种潜在的癌症治疗方法引起了广泛关注，它利用了肿瘤对铁需求的增加。本综述评估了铁螯合疗法对CRC进展的影响及其潜在机制。
对体内和体外研究进行了全面综述，以评估铁螯合疗法在CRC中的有效性。文献检索涵盖了1995年1月至2024年3月期间的PubMed、Scopus、Medline（通过Web of Science）和EMBASE。
多项体内和体外研究调查了铁螯合剂，如去铁胺、地拉罗司、硫代氨基脲类螯合剂、喹胺类螯合剂和其他新型化合物对CRC的影响。具有铁螯合特性的天然植物提取物也被探索作为潜在的治疗方法。大多数研究表明，铁螯合可以抑制结肠癌细胞的增殖，尽管一些研究表明有促癌作用。从机制上讲，铁螯合通过调节组蛋白甲基化、上调NDRG1以及影响Wnt/β-连环蛋白和p53信号通路来影响CRC的几个特征。然而，某些铁螯合剂可能抑制TRAIL介导的细胞凋亡并激活缺氧诱导因子（HIF），从而可能加速CRC进展。
未来在CRC中对铁螯合疗法的探索应集中在广泛的体外、体内和临床研究上，以阐明其中的确切机制。对铁螯合诱导的基因和细胞改变的更深入理解将促进CRC有效治疗策略的开发。
