Käpyaho K, Jänne J
Biochem Biophys Res Commun. 1983 May 31;113(1):18-23. doi: 10.1016/0006-291x(83)90425-4.
An exposure of cultured Cloudman S91 melanoma cells to inhibitors of polyamine biosynthesis, 2-difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone) (MGBG), distinctly promoted the expression of differentiated biochemical functions of the tumor cells. Slight to moderate growth inhibition produced by the compounds was associated with a stimulation of melanogenesis, as reflected by a striking enhancement of tyrosinase (EC 1.10.3.1) activity and an increase in cellular melanin content. Both antimetabolites acted synergistically with alpha-melanotropin (MSH), as regards the stimulation of melanogenesis. Exposure of the melanoma cells to MSH resulted in most experiments in a marked decrease of the intracellular polyamine pools, usually involving all three polyamines (putrescine, spermidine and spermine). The DFMO-induced stimulation of melanogenesis was totally suppressed by the administration of putrescine, whereas the MSH-stimulated tyrosinase activity was not influenced by the diamine. Although many recent reports indicate that terminal differentiation is accompanied by a distinct stimulation of polyamine biosynthesis, our results suggest that in certain cells polyamine deprivation may lead to an enhanced expression of differentiated phenotype.
将培养的Cloudman S91黑色素瘤细胞暴露于多胺生物合成抑制剂2-二氟甲基鸟氨酸（DFMO）和甲基乙二醛双（脒腙）（MGBG）中，明显促进了肿瘤细胞分化生化功能的表达。这些化合物产生的轻度至中度生长抑制与黑色素生成的刺激有关，这表现为酪氨酸酶（EC 1.10.3.1）活性显著增强以及细胞黑色素含量增加。就黑色素生成的刺激而言，这两种抗代谢物与α-促黑素（MSH）协同作用。在大多数实验中，将黑色素瘤细胞暴露于MSH会导致细胞内多胺池显著减少，通常涉及所有三种多胺（腐胺、亚精胺和精胺）。腐胺的施用完全抑制了DFMO诱导的黑色素生成刺激，而二胺对MSH刺激的酪氨酸酶活性没有影响。尽管最近许多报告表明终末分化伴随着多胺生物合成的明显刺激，但我们的结果表明，在某些细胞中，多胺缺乏可能导致分化表型的表达增强。
