Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Department of Chemistry & Biochemistry, California State University, Fullerton, 800 N. State College, Fullerton, CA 92834, United States.
Eur J Cell Biol. 2023 Sep;102(3):151337. doi: 10.1016/j.ejcb.2023.151337. Epub 2023 Jun 26.
Different studies corroborate a role for ceramide synthases and their downstream products, ceramides, in modulation of apoptosis and autophagy in the context of cancer. These mechanisms of regulation, however, appear to be context dependent in terms of ceramides' fatty acid chain length, subcellular localization, and the presence or absence of their downstream targets. Our current understanding of the role of ceramide synthases and ceramides in regulation of apoptosis and autophagy could be harnessed to pioneer the development of new treatments to activate or inhibit a single type of ceramide synthase, thereby regulating the apoptosis induction or cross talk of apoptosis and autophagy in cancer cells. Moreover, the apoptotic function of ceramide suggests that ceramide analogues can pave the way for the development of novel cancer treatments. Therefore, in the current review paper we discuss the impact of ceramide synthases and ceramides in regulation of apoptosis and autophagy in context of different types of cancers. We also briefly introduce the latest information on ceramide synthase inhibitors, their application in diseases including cancer therapy, and discuss approaches for drug discovery in the field of ceramide synthase inhibitors. We finally discussed strategies for developing strategies to use lipids and ceramides analysis in biological fluids for developing early biomarkers for cancer.
不同的研究证实了神经酰胺合酶及其下游产物神经酰胺在癌症中凋亡和自噬调节中的作用。然而，这些调节机制似乎依赖于神经酰胺的脂肪酸链长、亚细胞定位以及下游靶标的存在与否。我们目前对神经酰胺合酶和神经酰胺在凋亡和自噬调节中的作用的理解，可以用来开拓新的治疗方法的发展，以激活或抑制单一类型的神经酰胺合酶，从而调节癌细胞中的凋亡诱导或凋亡和自噬的串扰。此外，神经酰胺的凋亡功能表明神经酰胺类似物可以为开发新型癌症治疗方法铺平道路。因此，在当前的综述论文中，我们讨论了神经酰胺合酶和神经酰胺在不同类型癌症中调节凋亡和自噬的作用。我们还简要介绍了神经酰胺合酶抑制剂的最新信息，包括它们在癌症治疗等疾病中的应用，并讨论了神经酰胺合酶抑制剂领域的药物发现方法。最后，我们讨论了利用生物体液中的脂质和神经酰胺分析开发癌症早期生物标志物的策略。
