Medical University of South Carolina (MUSC), Division of Basic Sciences, Department of Biochemistry & Molecular Biology, 173 Ashley Avenue, MSC 504, Charleston, South Carolina 29425-5040, USA.
Expert Opin Ther Targets. 2009 Dec;13(12):1449-58. doi: 10.1517/14728220903357512.
Bioactive sphingolipids, such as ceramide, sphingosine and sphingosine-1-phosphate are known bio-effector molecules which play important roles in various aspects of cancer biology including cell proliferation, growth arrest, apoptosis, metastasis, senescence and inflammation. Therefore, enzymes involved in ceramide metabolism are gaining recognition as being critical regulators of cancer cell growth and/or survival. We previously observed that the ceramide metabolizing enzyme, acid ceramidase (AC) is upregulated in tumor tissues. Studies have now concluded that this creates a dysfunctional ceramide pathway, which is responsible for tumor progression and resistance to chemotherapy and radiation. This suggests that development of small-molecule drugs that inhibit AC enzyme activity is a promising approach for improving standard cancer therapy and patient's clinical outcomes.
生物活性神经酰胺,如神经酰胺、鞘氨醇和鞘氨醇-1-磷酸,是已知的生物效应分子,在癌症生物学的各个方面发挥着重要作用,包括细胞增殖、生长停滞、细胞凋亡、转移、衰老和炎症。因此,参与神经酰胺代谢的酶被认为是癌细胞生长和/或存活的关键调节剂。我们之前观察到,神经酰胺代谢酶酸性神经酰胺酶(AC)在肿瘤组织中上调。研究现已得出结论,这会导致神经酰胺途径功能失调,从而导致肿瘤进展以及对化疗和放疗的耐药性。这表明,开发抑制 AC 酶活性的小分子药物是改善标准癌症治疗和患者临床结果的一种很有前途的方法。