Scala Angela, Ficarra Silvana, Russo Annamaria, Barreca Davide, Giunta Elena, Galtieri Antonio, Grassi Giovanni, Tellone Ester
Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy.
Virology and Microbiology AOOR Papardo-Piemonte, V.le F. Stagno d'Alcontres, 98166 Messina, Italy.
Biochim Biophys Acta. 2015 Jan;1850(1):73-9. doi: 10.1016/j.bbagen.2014.09.022. Epub 2014 Sep 28.
The indole core is a key structural feature of many natural products and biomolecules with broad spectrum chemotherapeutic properties. Some of us have recently synthesized a library of biologically promising indolone-based compounds. The present study focuses on the effects of one of them, namely DPIT, on human erythrocytes.
We have examined the influence of DPIT on band 3 protein, intracellular ATP concentration and transport, caspase 3 activation, metabolic adaptation and membrane stability.
Our study elucidates that DPIT, intercalated into the phospholipid bilayer, decreases the anion transport, the intracellular ATP concentration and the cytosolic pH, inducing a direct activation of caspase 3.
Starting from the metabolic similarity between erythrocytes and cancer cells, we investigate how the metabolic derangements and membrane alterations induced by selected heterocycles could be related to the antiproliferative effects.
Our work aims to propose a new model of study to predict the antiproliferative effects of heterocyclic scaffolds, pointing out that only one of the listed conditions would be unfavorable to the life cycle of neoplastic cells.
吲哚核心是许多具有广谱化疗特性的天然产物和生物分子的关键结构特征。我们中的一些人最近合成了一系列具有生物学前景的吲哚酮类化合物。本研究聚焦于其中一种化合物，即DPIT，对人红细胞的影响。
我们研究了DPIT对带3蛋白、细胞内ATP浓度及转运、半胱天冬酶3激活、代谢适应和膜稳定性的影响。
我们的研究表明，插入磷脂双分子层的DPIT会降低阴离子转运、细胞内ATP浓度和胞质pH值，直接激活半胱天冬酶3。
基于红细胞与癌细胞之间的代谢相似性，我们研究了特定杂环化合物诱导的代谢紊乱和膜改变如何与抗增殖作用相关。
我们的工作旨在提出一种新的研究模型，以预测杂环支架的抗增殖作用，指出所列条件中只有一种不利于肿瘤细胞的生命周期。
