Bioactive sphingolipids in docetaxel-induced apoptosis in human prostate cancer cells

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• 作者：Esen Yonca Bassoy ; Yusuf Baran ; ^{yusufbaran@iyte.edu} ; ^{triytecancer@gmail.com}
• 关键词：Prostate cancer ; Bioactive sphingolipids ; Ceramides ; Sphingosine kinase ; Glucosyle ceramide synthase ; Docetaxel
• 刊名：Biomedicine and Pharmacotherapy
• 出版年：2012
• 期刊代码：36_07533322
• 类别：med
• 出版时间：March, 2012
• 卷：66
• 期：2
• 页码：103-110
• 文件大小：1450 K

摘要

In this study, we examined the possible roles of ceramide/sphingosine-1-phosphate and ceramide/glucosyleceramide signaling in docetaxel-induced apoptosis by examining expression levels of the glucosyleceramide synthase and sphingosine kinase-1 and ceramide synthase gene family. As confirmed by isobologram analysis, docetaxel in combination with agents that increase intracellular ceramide levels increased the cytotoxic and apoptotic effects of docetaxel synergistically. More importantly, RT-PCR results revealed that expression levels of glucosyleceramide synthase and sphingosine kinase-1 were downregulated and ceramide synthase genes were upregulated in response to docetaxel. This study identifies mechanisms underlying the involvement of ceramide metabolizing genes in docetaxel-induced apoptosis in prostate cancer cells.