Departamento de Morfologia y Biologia Celular, Instituto Universitario Oncologico del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain.
Departamento de Quimica Fisica y Analitica, Universidad de Oviedo, 33006 Oviedo, Spain.
Int J Mol Sci. 2017 Jul 26;18(8):1620. doi: 10.3390/ijms18081620.
The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the "Warburg effect" only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type.
松果腺神经内分泌褪黑素发挥着非凡的全身功能。其中一些功能是通过其特定的膜受体 1 型和 2 型（MT1 和 MT2）发挥的，而其他功能则是通过受体非依赖性机制介导的。有人提出褪黑素可能通过易化葡萄糖转运蛋白（GLUT/）进行转运。前列腺细胞具有特殊的代谢方式，在肿瘤进展过程中会发生变化。在癌变的最初阶段，氧化磷酸化被重新激活，而只有在晚期肿瘤和转移阶段才会发生向“Warburg 效应”的转变。在这里，我们研究了褪黑素是否可能改变前列腺癌细胞的代谢。为此，我们在雄激素敏感的 LNCaP 和不敏感的 PC-3 前列腺癌细胞中使用了 C 稳定同位素分辨代谢组学。除了代谢物 C 标记物、ATP/AMP 水平以及乳酸脱氢酶或戊糖磷酸途径活性的测量外。褪黑素降低了雄激素敏感细胞中乳酸的标记，也降低了三羧酸循环代谢物和 ATP 产生的 C 标记。此外，褪黑素还降低了雄激素不敏感前列腺癌细胞中乳酸的 C 标记。结果表明，褪黑素限制了前列腺癌细胞中的糖酵解以及三羧酸循环和戊糖磷酸途径，这表明在这种肿瘤类型中，减少葡萄糖摄取是该吲哚的主要靶标。
