Spanish National Research Council, Research Unit on Bioactive Molecules, Departament de Química Biomèdica, Institut de Química Avançada de Catalunya, Barcelona, Spain.
Anticancer Agents Med Chem. 2011 Nov;11(9):830-43. doi: 10.2174/187152011797655104.
Ceramidases are ubiquitous amidohydrolases that catalyze the cleavage of ceramides into sphingosine and fatty acids. This reaction exerts a cytoprotective role in physiological conditions, while altered ceramidase activities favour a number of human diseases. Among these diseases, several reports point to important roles of ceramidases, mainly the acid ceramidase, in the initiation and progression of cancer, and the response of tumors to radio- or chemotherapy. Multiple reports confirm the interest of acid ceramidase inhibitors as anticancer drugs, either alone or in combination with other therapies. Sphingolipid metabolism plays a role in hematological malignancies and appears as an interesting target for therapeutic intervention. Although the use of ceramidase inhibitors in chemotherapy of hematologic cancers has not been widely investigated, a number of indirect evidence suggest that inhibition of specific ceramidases could potentiate the effect of drugs in clinical use to treat hematologic malignancies and may afford strategies to combat relapses. The arsenal of ceramidase inhibitors so far available is wide and hopefully, upcoming research will assess the feasibility of this approach.
神经酰胺酶是一种广泛存在的酰胺水解酶，能够催化神经酰胺分解为神经鞘氨醇和脂肪酸。在生理条件下，这种反应具有细胞保护作用，而神经酰胺酶活性的改变则有利于多种人类疾病的发生。在这些疾病中，有多项报道指出神经酰胺酶（主要是酸性神经酰胺酶）在癌症的发生和发展，以及肿瘤对放射或化学疗法的反应中起着重要作用。多项报道证实了酸性神经酰胺酶抑制剂作为抗癌药物的应用价值，无论是单独使用还是与其他疗法联合使用。鞘脂代谢在血液恶性肿瘤中发挥作用，是一种很有前途的治疗干预靶点。尽管神经酰胺酶抑制剂在血液系统恶性肿瘤的化疗中的应用尚未得到广泛研究，但有许多间接证据表明，抑制特定的神经酰胺酶可以增强临床使用的药物治疗血液系统恶性肿瘤的效果，并可能为对抗复发提供策略。迄今为止，神经酰胺酶抑制剂的种类繁多，希望未来的研究能够评估这种方法的可行性。
