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• W2058883888 abstract "The prevailing mechanisms of action of traditional chemotherapeutic agents have been challenged by sphingolipid cancer research. Many studies have shown that ceramide generation in response to cytotoxic agents is central to tumor cell death. Ceramide can be generated either via hydrolysis of cell-membrane sphingomyelin by sphingomyelinases, hydrolysis of cerebrosides, or via de novo synthesis by ceramide synthases. Ceramide can act as a second messenger for apoptosis, senescence or autophagy. Inherent or acquired alterations in the sphingolipid pathway can account for resistance to the classic chemotherapeutic agents. In particular, it has been shown that activation of the acid ceramidase can lead to the formation of sphingosine 1-phosphate, which then antagonizes ceramide signaling by initiating a pro-survival signaling pathway. Furthermore, ceramide glycosylation catalyzed by glucosylceramide synthase converts ceramide to glucosylceramide, thus eliminating ceramide and consequently protecting cancer cells from apoptosis. In this review, we describe the effects of some of the most commonly used chemotherapeutic agents on ceramide generation, with a particular emphasis on strategies used to enhance the efficacy of these agents." @default.
• W2058883888 created "2016-06-24" @default.
• W2058883888 creator A5039007636 @default.
• W2058883888 creator A5062197734 @default.
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• W2058883888 date "2015-06-01" @default.
• W2058883888 modified "2023-10-13" @default.
• W2058883888 title "Novel mechanisms of action of classical chemotherapeutic agents on sphingolipid pathways" @default.
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• W2058883888 doi "https://doi.org/10.1515/hsz-2014-0302" @default.
• W2058883888 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25719313" @default.
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