Kingsnorth A N
Ann R Coll Surg Engl. 1986 Mar;68(2):76-81.
The polyamines, putrescine, spermidine and spermine are small cationic molecules essential for DNA synthesis and cell replication. Because the cytotoxicity of most anti-cancer drugs can be attributed to inhibitory effects on DNA synthesis and cell replication it led to speculation that inhibition of polyamine synthesis could be a useful tool in the control of neoplastic growth. In 1978 alpha-difluoromethylornithine (DFMO), a powerful inhibitor of ornithine decarboxylase, the rate limiting enzyme in polyamine synthesis, was synthesized by Metcalf. Since then numerous investigators have tested the potential of DFMO and other polyamine antimetabolites as chemotherapeutic agents in experimental animals and cell cultures. The accumulated knowledge is now being evaluated in the treatment of human proliferative disorders and cancer.
多胺、腐胺、亚精胺和精胺是DNA合成和细胞复制所必需的小分子阳离子。由于大多数抗癌药物的细胞毒性可归因于对DNA合成和细胞复制的抑制作用,因此有人推测抑制多胺合成可能是控制肿瘤生长的一种有用工具。1978年,甲硫氨酸合成了α-二氟甲基鸟氨酸(DFMO),一种鸟氨酸脱羧酶(多胺合成中的限速酶)的强效抑制剂。从那时起,众多研究人员在实验动物和细胞培养中测试了DFMO和其他多胺抗代谢物作为化疗药物的潜力。目前正在评估这些积累的知识在治疗人类增殖性疾病和癌症方面的应用。