Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.
Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.
Biomolecules. 2021 Jul 16;11(7):1049. doi: 10.3390/biom11071049.
Cyclooxygenase-2 (COX-2) is an important enzyme involved in prostaglandins biosynthesis from arachidonic acid. COX-2 is frequently overexpressed in human cancers and plays a major tumor promoting function. Accordingly, many efforts have been devoted to efficiently target the catalytic site of this enzyme in cancer cells, by using COX-2 specific inhibitors such as celecoxib. However, despite their potent anti-tumor properties, the myriad of detrimental effects associated to the chronic inhibition of COX-2 in healthy tissues, has considerably limited their use in clinic. In addition, increasing evidence indicate that these anti-cancerous properties are not strictly dependent on the inhibition of the catalytic site. These findings have led to the development of non-active COX-2 inhibitors analogues aiming at preserving the antitumor effects of COX-2 inhibitors without their side effects. Among them, two celecoxib derivatives, 2,5-Dimethyl-Celecoxib and OSU-03012, have been developed and suggested for the treatment of viral (e.g., recently SARS-CoV-2), inflammatory, metabolic diseases and cancers. These molecules display stronger anti-tumor properties than celecoxib and thus may represent promising anti-cancer molecules. In this review, we discuss the impact of these two analogues on cancerous processes but also their potential for cancer treatment alone or in combination with existing approaches.
环氧化酶-2（COX-2）是参与花生四烯酸合成前列腺素的重要酶。COX-2 在人类癌症中经常过表达，并发挥主要的肿瘤促进功能。因此，许多努力都致力于通过使用 COX-2 特异性抑制剂（如塞来昔布）来有效地靶向癌细胞中该酶的催化位点。然而，尽管它们具有很强的抗肿瘤特性，但由于 COX-2 在健康组织中的慢性抑制相关的多种有害影响，它们在临床上的应用受到了极大限制。此外，越来越多的证据表明，这些抗癌特性并不严格依赖于催化位点的抑制。这些发现导致了非活性 COX-2 抑制剂类似物的开发，旨在在不产生副作用的情况下保留 COX-2 抑制剂的抗肿瘤作用。其中，两种塞来昔布衍生物，2,5-二甲基塞来昔布和 OSU-03012，已经被开发出来，并被建议用于治疗病毒（例如最近的 SARS-CoV-2）、炎症、代谢疾病和癌症。这些分子显示出比塞来昔布更强的抗肿瘤特性，因此可能代表有前途的抗癌分子。在这篇综述中，我们讨论了这两种类似物对癌症过程的影响，但也讨论了它们单独或与现有方法联合用于癌症治疗的潜力。
