Abstract
Acute myeloid leukemia (AML) is a heterogeneous myeloid clonal disorder exhibiting the accumulation of immature myeloid progenitors in the bone marrow and peripheral blood. Standard AML therapy requires intensive combination chemotherapy, which leads to significant treatment-related toxicity. The search for new, low toxic marine agents, inducing the generation of ceramide in leukemic cells is a new approach to improve the therapy of leukemia. This review focuses on the metabolism of sphingolipids, the role of ceramide in treating leukemia, and the antitumor activity, related to ceramide metabolism, of some marine metabolites, particularly stichoposides, triterpene glycosides extracted from sea cucumbers of the family Stichopodiidae.
Highlights
Sphingolipids have been recognized as bioactive lipids involved in the regulation of various cell functions, including cell death, proliferation/survival, autophagy, migration, secretion and immunity [1,2,3]
Yun et al firstly demonstrated that stichoposide D (STD) can induce apoptosis of leukemia cells through the activation of CerS6 leading to increased ceramide levels [67]
It has been shown that some marine natural products and stichoposides from sea cucumbers have antitumor activity through the generation of ceramide
Summary
Sphingolipids have been recognized as bioactive lipids involved in the regulation of various cell functions, including cell death, proliferation/survival, autophagy, migration, secretion and immunity [1,2,3]. It was first reported that ceramide induced cell differentiation and death in human leukemia HL-60 cells [4,5]. Several marine metabolites are known to induce the generation of ceramide in tumor cells, including triterpene glycosides, which are widely distributed in plants and found in marine invertebrates [8]. Many marine triterpene glycosides are good sources for developing anticancer agents because of low toxicity suitable for administration, promising activities and wide diversity in their mechanisms of action. This review highlights our current understanding of the metabolism of sphingolipids, the tumor suppressive functions of ceramide, and the action mechanisms of stichoposides related to ceramide metabolism in treating leukemia. Some data on other marine inducers of ceramide accumulation in tumor cells are given.
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