Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Curr Mol Pharmacol. 2008 Jan;1(1):50-60. doi: 10.2174/1874467210801010050.
The natural compounds that interfere with cellular DNA such as enediyne antitumor antibiotics might be important chemotherapeutic agents for the treatment of cancer. In this article, the pharmacology and anticancer activity of the enediyne antitumor agents that are approved for clinical use and undergoing pre-clinical or clinical evaluation are reviewed. Most enediyne compounds have shown potent activity against the proliferation of various cancer cells, including cells that display resistance to other chemotherapeutic drugs. Enediyne derivatives, such as an immunoconjugate composed of an enediyne compound and monoclonal antibody, reveal stronger activity and selectivity for human cancer cells. The mechanism underlying the anticancer activity of these enediyne antitumor agents may mainly lie in their generation of DNA double-strand breaks. Increasing evidence shows that the enediyne-induced DNA double-strand breaks can engage the activation of DNA damage response proteins, arresting cell cycle progression and eventually leading to apoptotic cell death. Continued investigation of the mechanisms of action and development of new enediyne derivatives and conjugates may provide more effective therapeutics for cancer treatments.
干扰细胞 DNA 的天然化合物，如烯二炔类抗肿瘤抗生素，可能是治疗癌症的重要化疗药物。本文综述了已批准临床应用和正在进行临床前或临床评价的烯二炔类抗肿瘤药物的药理学和抗肿瘤活性。大多数烯二炔化合物对各种癌细胞的增殖均显示出很强的活性，包括对其他化疗药物耐药的细胞。烯二炔衍生物，如由烯二炔化合物和单克隆抗体组成的免疫偶联物，对人癌细胞显示出更强的活性和选择性。这些烯二炔类抗肿瘤药物的抗肿瘤活性的机制可能主要在于它们产生 DNA 双链断裂。越来越多的证据表明，烯二炔诱导的 DNA 双链断裂可激活 DNA 损伤反应蛋白，阻止细胞周期进程，最终导致细胞凋亡。对作用机制的进一步研究以及新型烯二炔衍生物和偶联物的开发，可能为癌症治疗提供更有效的治疗方法。
