EFFECTS OF MELATONIN ON THE CELL-CYCLE KINETICS AND ESTROGEN-RESCUE OF MCF-7 HUMAN BREAST-CANCER CELLS IN CULTURE
EFFECTS OF MELATONIN ON THE CELL-CYCLE KINETICS AND ESTROGEN-RESCUE OF MCF-7 HUMAN BREAST-CANCER CELLS IN CULTURE
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DOI：
10.1111/j.1600-079x.1991.tb00007.x
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发表时间：
1991-01-01
影响因子：
10.3
通讯作者：
HILL, AB
中科院分区：
文献类型：
--
作者：
COS, S;BLASK, DE;HILL, AB
褪黑激素已被证明对培养的雌激素反应性 MCF-7 人乳腺癌细胞的增殖具有直接抑制作用。在本研究中，我们通过流式细胞术检查了这种抑制作用是否可能作用于细胞周期的G1期，从而导致向S期的转变延迟。为了进一步验证这一假设，我们测试了雌二醇从褪黑激素抑制中“拯救”MCF-7细胞的能力，以及这种吲哚胺阻断雌二醇从他莫昔芬抑制中拯救细胞的能力的潜力。孵育五天后，褪黑激素 (10(-9)M) 增加了细胞周期 G1 期细胞的比例，同时导致 S 期细胞比例减少 50%。在克隆软琼脂培养物中同时用雌二醇(10(-8)M)处理细胞可以阻止褪黑素(10(-5)M)的抗增殖作用，或者通过在单层培养物中向先前与褪黑素(10(-9)M)一起孵育并被褪黑素(10(-9)M)抑制的细胞中添加雌二醇来逆转。此外，在两种类型的培养系统中，褪黑激素阻断了他莫昔芬抑制细胞的雌激素救援。这些结果支持这样的假设：褪黑激素的抗增殖作用（如他莫昔芬）通过引起 G1-S 转变延迟而具有细胞周期特异性。这些结果还表明褪黑激素与雌激素介导的 MCF-7 细胞增殖机制之间存在重要的相互作用。
Melatonin has been shown to have a direct inhibitory action on the proliferation of estrogen-responsive MCF-7 human breast cancer cells in culture. In the present study, we examined by flow cytometry whether this inhibitory effect might be exerted on the G1 phase of the cell cycle, thus causing a transition delay into the S phase. In order to further verify this hypothesis we tested the ability of estradiol to "rescue" MCF-7 cells from melatonin inhibition, and the potential of this indoleamine to block the ability of estradiol to rescue the cells from tamoxifen inhibition. Following five days of incubation, melatonin (10(-9)M) increased the fraction of cells in G1 of the cell cycle while simultaneously causing a 50% reduction in the proportion of cells in S phase. The antiproliferative effect of melatonin (10(-5)M) was prevented by the simultaneous treatment of the cells with estradiol (10(-8)M) in clonogenic soft agar culture, or reversed by the addition of estradiol to cells previously incubated with and inhibited by melatonin (10(-9)M) in monolayer culture. Additionally, melatonin blocked the estrogen-rescue of tamoxifen-inhibited cells in both types of culture systems. These results support the hypothesis that the antiproliferative effect of melatonin, like tamoxifen, is cell cycle specific by causing a G1-S transition delay. These results also indicate an important interaction of melatonin with estrogen-mediated mechanisms of MCF-7 cell proliferation.