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多胺抗代谢物的化疗潜力。

The chemotherapeutic potential of polyamine antimetabolites.

作者信息

Kingsnorth A N

出版信息

Ann R Coll Surg Engl. 1986 Mar;68(2):76-81.

PMID:3082276
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2497796/
Abstract

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.

摘要

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。

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本文引用的文献

1
The Isolation of Spermine Phosphate from Semen and Testis.从精液和睾丸中分离磷酸精胺。
Biochem J. 1924;18(6):1253-1262.1. doi: 10.1042/bj0181253.
2
X-RAY STUDY OF SPERMINE TETRAHYDROCHLORIDE.盐酸精胺的X射线研究
J Mol Biol. 1965 Feb;11:438-40. doi: 10.1016/s0022-2836(65)80069-9.
3
In vitro induction of ornithine decarboxylase in urinary bladder carcinoma cells.体外诱导膀胱癌细胞中的鸟氨酸脱羧酶
Cancer Res. 1981 Feb;41(2):405-9.
4
Ornithine decarboxylase enzyme activity in human and hamster pancreatic tumor cell lines.人和仓鼠胰腺肿瘤细胞系中的鸟氨酸脱羧酶活性
Cancer Lett. 1982 Oct;17(1):87-93. doi: 10.1016/0304-3835(82)90113-6.
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Polyamine biosynthesis and interconversion in rodent tissues.啮齿动物组织中的多胺生物合成与相互转化
Fed Proc. 1982 Dec;41(14):3065-72.
6
alpha-Difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, inhibits tumor promoter-induced polyamine accumulation and carcinogenesis in mouse skin.α-二氟甲基鸟氨酸是鸟氨酸脱羧酶的不可逆抑制剂，可抑制肿瘤启动子诱导的小鼠皮肤多胺积累和致癌作用。
Proc Natl Acad Sci U S A. 1982 Oct;79(19):6028-32. doi: 10.1073/pnas.79.19.6028.
7
An essential role for polyamines in tumor metastases.多胺在肿瘤转移中起重要作用。
FEBS Lett. 1982 Dec 27;150(2):397-9. doi: 10.1016/0014-5793(82)80775-8.
8
Polyamine metabolism and function.多胺代谢与功能。
Am J Physiol. 1982 Nov;243(5):C212-21. doi: 10.1152/ajpcell.1982.243.5.C212.
9
Effects of DL-alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, on the rat mammary tumour induced by 7,12-dimethylbenz[a]anthracene.鸟氨酸脱羧酶不可逆抑制剂DL-α-二氟甲基鸟氨酸对7,12-二甲基苯并[a]蒽诱导的大鼠乳腺肿瘤的影响。
Naunyn Schmiedebergs Arch Pharmacol. 1982 Jul;320(1):72-7. doi: 10.1007/BF00499076.
10
Polyamine depletion influences drug-induced chromosomal damage.多胺耗竭影响药物诱导的染色体损伤。
Science. 1982 Sep 10;217(4564):1044-6. doi: 10.1126/science.6810463.

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