Apomorphine, dopamine and phenylethylamine reduce the proportion of phosphorylated insulin receptor substrate 1
Apomorphine, dopamine and phenylethylamine reduce the proportion of phosphorylated insulin receptor substrate 1
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DOI：
10.1016/s0014-2999(01)01491-1
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发表时间：
2001-12-14
影响因子：
5
通讯作者：
Maggio, R
中科院分区：
文献类型：
--
作者：
Chiarenza, A;Scarselli, M;Maggio, R
我们测试了多巴胺、阿扑吗啡、苯乙胺和培高利特抑制胎牛血清刺激的人乳腺癌（MCF）-7细胞增殖的能力。虽然前三种化合物能够阻断MCF-7细胞的增殖，但培高利特不能做到这一点（高达100 μ M）。多巴胺、阿扑吗啡和苯乙胺的抑制作用在血清饥饿胰岛素刺激的MCF-7细胞中也是明显的。阿扑吗啡还抑制人雌激素受体阴性乳腺癌（MDA-MB 231）和前列腺癌（LNCaP）细胞系的增殖。在第二组实验中，我们测量了多巴胺、阿扑吗啡、苯乙胺和培高利特抑制胰岛素受体底物（IRS）-1（胰岛素样生长因子（IGF）-1受体的主要细胞内底物）磷酸化（或增加去磷酸化）的能力。多巴胺、阿扑吗啡和苯乙胺都将磷酸化IRS-1的水平降低到零，效力范围在0.01和1 μ M之间。最后，我们发现，与野生型小鼠的成纤维细胞相比，IRS-1缺失（-/-）小鼠的成纤维细胞对阿扑吗啡的抗增殖作用不太敏感，这表明阿扑吗啡对IRS-1磷酸化的抑制是该化合物活性的一个重要方面。(C)2001年爱思唯尔科学B.V所有比赛保留。
We tested the ability of dopamine, apomorphine, phenylethylamine and pergolide to inhibit the proliferation of fetal calf serum-stimulated human breast cancer (MCF)-7 cells. While the first three compounds were able to block the proliferation of MCF-7 cells, pergolide failed to do so (up to 100 muM). The inhibitory effect of dopamine, apomorphine and phenylethylamine was also evident in serum-starved insulin-stimulated MCF-7 cells. Apomorphine also inhibited the proliferation of the human oestrogen receptor-negative breast cancer (MDA-MB231) and prostate carcinoma (LNCaP) cell lines. In a second set of experiments, we measured the ability of dopamine, apomorphine, phenylethylamine and pergolide to inhibit the phosphorylation (or increase the dephosphorylation) of the insulin receptor substrate (IRS)-1, a major intracellular substrate of the insulin-like growth factor (IGF)-1 receptor. Dopamine, apomorphine and phenylethylamine all reduced to zero the level of phosphorylated IRS-1 with potencies ranging between 0.01 and 1 muM. Finally, we found that fibroblasts from IRS-1 null (-/-) mice were less sensitive to the anti-proliferative effect of apomorphine compared to fibroblasts from wild type-mice, suggesting that the inhibition of IRS-1 phosphorylation by apomorphine is an important aspect of the activity of this compound. (C) 2001 Elsevier Science B.V All fights reserved.