Effects of inhibitors of polyamine biosynthesis on the growth and melanogenesis of murine melanoma cells.
Effects of inhibitors of polyamine biosynthesis on the growth and melanogenesis of murine melanoma cells.
复制标题
多胺生物合成抑制剂对小鼠黑色素瘤细胞生长和黑色素生成的影响。
作者：
K. Käpyaho;R. Sinervirta;J. Jänne
鸟氨酸脱羧酶的不可逆抑制剂2-二氟甲基鸟氨酸（DFMO）（EC 4.1.1.17）和S-腺苷甲硫氨酸脱羧酶的竞争性抑制剂甲基乙二醛双（鸟苷酰腙）（MGBG）（EC 4.1.1.50）均显著刺激鼠Cloudman S91黑素瘤细胞的黑素表达。DFMO对酪氨酸酶（EC 1.10.3.1）活性和黑色素形成的刺激与响应药物而产生的腐胺和亚精胺的细胞内消耗密切相关。然而，很少或没有证据表明，增强的黑素生成响应MGBG介导的多胺生物合成的抑制。鸟氨酸脱羧酶的间接抑制剂，如1，3-二氨基丙烷和1，3-二氨基丙-2-醇，但不是腐胺，同样抑制黑色素瘤细胞的生长，并刺激其黑色素的产生。与α-促黑素激素引起的效果相反，多胺抗代谢物对黑素生成的刺激不是由环腺苷3 '：5'-单磷酸介导的。MGBG或二胺也不太可能充当能够原位刺激酪氨酸酶活性的溶酶体促动剂，因为无论在培养细胞中还是使用无细胞匀浆中测定，酶活性都被药物刺激。没有一种药物在体外刺激酪氨酸酶活性。DFMO和MGBG对黑色素瘤细胞增殖的影响是可逆的，但恢复正常生长和黑色素形成，特别是在暴露于DFMO的细胞中，是非常缓慢的。目前的结果代表了进一步的实验模型，其中多胺积累的抑制伴随着终末分化的迹象。
Both 2-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (EC 4.1.1.17), and methylglyoxal bis(guanylhydrazone) (MGBG), a competitive inhibitor of S-adenosylmethionine decarboxylase (EC 4.1.1.50), strikingly stimulated melanotic expression of murine Cloudman S91 melanoma cells. The stimulation of tyrosinase (EC 1.10.3.1) activity and melanin formation by DFMO was closely associated with intracellular depletion of putrescine and spermidine developed in response to the drug. However, little or no evidence was obtained indicating that enhanced melanogenesis in response to MGBG was mediated through an inhibition of polyamine biosynthesis. Indirect inhibitors of ornithine decarboxylase, such as 1,3-diaminopropane and 1,3-diaminopropan-2-ol, but not putrescine, likewise inhibited the growth of the melanoma cells and stimulated their melanin production. The stimulation of melanogenesis by polyamine antimetabolites was not mediated by cyclic adenosine 3':5'-monophosphate, in contrast to the effect elicited by alpha-melanotropin. It is also unlikely that MGBG or the diamines acted as lysosomotropic agents capable of stimulating tyrosinase activity in situ, since the enzyme activity was stimulated by the drugs irrespective of whether assayed in cultured cells or using cell-free homogenates. None of the agents stimulated tyrosinase activity in vitro. The effect of DFMO and MGBG on melanoma cell proliferation was reversible, but the restoration of normal growth and melanin formation, especially in cells exposed to DFMO, was remarkably slow. The present results represent a further experimental model, in which the inhibition of polyamine accumulation is accompanied by signs of terminal differentiation.
影响因子：
56.9
作者：
KORNER, A;PAWELEK, J
通讯作者：
PAWELEK, J
多胺消耗抑制 L6 成肌细胞的分化。
DOI：
10.1016/0006-291x(83)90651-4
发表时间：
1983
影响因子：
3.1
作者：
Erwin,BG;Ewton,DZ;Florini,JR;Pegg,AE
通讯作者：
Pegg,AE
多胺生物合成在人类粒细胞分化过程中发挥重要作用。
影响因子：
11.2
作者：
Verma,DS;Sunkara,PS
通讯作者：
Sunkara,PS