Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
Future Med Chem. 2013 Aug;5(12):1405-21. doi: 10.4155/fmc.13.107.
Ceramide serves as a central mediator in sphingolipid metabolism and signaling pathways, regulating many fundamental cellular responses. It is referred to as a 'tumor suppressor lipid', since it powerfully potentiates signaling events that drive apoptosis, cell cycle arrest, and autophagic responses. In the typical cancer cell, ceramide levels and signaling are usually suppressed by overexpression of ceramide-metabolizing enzymes or downregulation of ceramide-generating enzymes. However, chemotherapeutic drugs as well as radiotherapy increase intracellular ceramide levels, while exogenously treating cancer cells with short-chain ceramides leads to anticancer effects. All evidence currently points to the fact that the upregulation of ceramide levels is a promising anticancer strategy. In this review, we exhibit many anticancer ceramide analogs as downstream receptor agonists and ceramide-metabolizing enzyme inhibitors.
神经酰胺作为鞘脂代谢和信号通路的中心介质，调节许多基本的细胞反应。它被称为“肿瘤抑制脂质”，因为它有力地增强了驱动细胞凋亡、细胞周期停滞和自噬反应的信号事件。在典型的癌细胞中，神经酰胺水平和信号通常被神经酰胺代谢酶的过表达或神经酰胺生成酶的下调所抑制。然而，化疗药物和放疗会增加细胞内神经酰胺水平，而用短链神经酰胺外源处理癌细胞则会产生抗癌作用。目前所有的证据都表明，上调神经酰胺水平是一种有前途的抗癌策略。在这篇综述中，我们展示了许多作为下游受体激动剂和神经酰胺代谢酶抑制剂的抗癌神经酰胺类似物。
