Bioactive sphingolipids in docetaxel-induced apoptosis in human prostate cancer cells.
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.
Izmir Institute of Technology, Department of Molecular Biology and Genetics, Cancer Genetics and Molecular Hematology Laboratory, 35430, Urla, Izmir, Turkey.
Esen Yonca
EY
Bassoy
Yusuf
Y
Baran
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism; D000077143:Docetaxel; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005963:Glucosylceramides / Q000378:metabolism; D005964:Glucosyltransferases / Q000235:genetics; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D010088:Oxidoreductases / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D000099157:Sphingosine Kinase
D000970:Antineoplastic Agents; D002518:Ceramides; D000077143:Docetaxel; D005963:Glucosylceramides; D005964:Glucosyltransferases; D008246:Lysophospholipids; D010088:Oxidoreductases; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D043823:Taxoids; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate; C108138:dihydroceramide desaturase; C023246:ceramide glucosyltransferase