α-Difluoromethylornithine-Induced Cytostasis is Reversed by Exogenous Polyamines, Not by Thymidine Supplementation.
α-Difluoromethylornithine-Induced Cytostasis is Reversed by Exogenous Polyamines, Not by Thymidine Supplementation.
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α-二氟甲基鸟氨酸诱导的细胞稳定可被外源性多胺逆转，而不是通过补充胸苷来逆转。
DOI：
10.3390/biom11050707
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发表时间：
2021-05-10
期刊：
影响因子：
5.5
通讯作者：
Keinänen TA
中科院分区：
文献类型：
--
作者：
Hyvönen MT;Khomutov M;Vepsäläinen J;Khomutov AR;Keinänen TA
多胺亚精胺是真核细胞增殖所必需的。多胺生物合成抑制剂α-二氟甲基鸟氨酸（DFMO）的给药可诱导细胞停滞，其发生在两个阶段;早期阶段可被亚精胺、精胺及其类似物逆转，晚期阶段的特征是细胞亚精胺库几乎完全耗尽。细胞在晚期的生长可以被亚精胺和极少数的类似物逆转，包括（S）-1-甲基亚精胺。先前报道（Witherspoon等Cancer Discovery 3（9）; 1072-81，2013）DFMO处理导致细胞胸苷库的耗尽，并且外源性胸苷补充部分地防止DFMO诱导的细胞停滞，而不影响HT-29、SW 480和LoVo结肠直肠癌细胞中的细胞内多胺库。在此，我们发现胸苷不能阻止DU 145、LNCaP、MCF 7、CaCo 2、BT 4C、SV 40 MES 13、HepG 2、HEK 293、NIH 3 T3、ARPE 19或HT-29细胞系中DFMO诱导的细胞停滞，而给予亚精胺的功能活性模拟物（S）-1-甲基亚精胺则可以。因此，胸苷的作用似乎仅对某些细胞系具有特异性。我们的结论是，降低多胺水平，也可能扭曲池叶酸依赖性代谢物介导的DFMO的抗增殖作用。然而，多胺是必要的，足以克服DFMO诱导的细胞停滞，而胸苷一般不是。
Polyamine spermidine is essential for the proliferation of eukaryotic cells. Administration of polyamine biosynthesis inhibitor α-difluoromethylornithine (DFMO) induces cytostasis that occurs in two phases; the early phase which can be reversed by spermidine, spermine, and some of their analogs, and the late phase which is characterized by practically complete depletion of cellular spermidine pool. The growth of cells at the late phase can be reversed by spermidine and by very few of its analogs, including (S)-1-methylspermidine. It was reported previously (Witherspoon et al. Cancer Discovery 3(9); 1072–81, 2013) that DFMO treatment leads to depletion of cellular thymidine pools, and that exogenous thymidine supplementation partially prevents DFMO-induced cytostasis without affecting intracellular polyamine pools in HT-29, SW480, and LoVo colorectal cancer cells. Here we show that thymidine did not prevent DFMO-induced cytostasis in DU145, LNCaP, MCF7, CaCo2, BT4C, SV40MES13, HepG2, HEK293, NIH3T3, ARPE19 or HT-29 cell lines, whereas administration of functionally active mimetic of spermidine, (S)-1-methylspermidine, did. Thus, the effect of thymidine seems to be specific only for certain cell lines. We conclude that decreased polyamine levels and possibly also distorted pools of folate-dependent metabolites mediate the anti-proliferative actions of DFMO. However, polyamines are necessary and sufficient to overcome DFMO-induced cytostasis, while thymidine is generally not.
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影响因子：
3.5
作者：
Park, M. H.;Nishimura, K.;Zanelli, C. F.;Valentini, S. R.
通讯作者：
Valentini, S. R.
影响因子：
4.6
作者：
Pegg, Anthony E.
通讯作者：
Pegg, Anthony E.
影响因子：
3.5
作者：
Hyvonen, Mervi T.;Keinanen, Tuomo A.;Khomutov, Maxim;Simonian, Alina;Vepsalainen, Jouko;Park, Jong Hwan;Khomutov, Alex R.;Alhonen, Leena;Park, Myung Hee
通讯作者：
Park, Myung Hee
DOI：
10.1016/j.biocel.2003.11.016
发表时间：
2004-11-01
影响因子：
4
作者：
Avila, MA;García-Trevijano, ER;Mato, JM
通讯作者：
Mato, JM
影响因子：
4.8
作者：
Hyvonen, Mervi T.;Keinanen, Tuomo A.;Janne, Juhani
通讯作者：
Janne, Juhani