Interrelation of differentiation, proliferation and apoptosis in cancer cells.
Treatment of human leukemia HL-60 cells with ceramide, a breakdown product of sphingomyelin, induced both programmed cell death ("apoptosis"), and cellular differentiation. Apoptosis in response to ceramide occurred in a concentration-dependent manner. Apoptosis induced by ceramide in HL-60 cells requires the presence of c-jun protooncogene. However apoptosis is inhibited by curcumin, a specific inhibitor of c-jun/AP-1. Whereas curcumin restores ability of inhibited cells to grow, it does not affect ceramide-induced differentiation. These results indicate that ceramide controls cell differentiation and proliferation through apoptosis by activating the nuclear transcriptional factor AP-1. Further, AP-1 is apparently more closely related to apoptosis-inducing signal transduction pathway than to the pathway leading to cellular differentiation.
Yamamoto
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Graduate School of Dentistry (Oral and Maxillofacial Surgery), Osaka Dental University, Japan.
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002518:Ceramides / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000096:biosynthesis* / Q000235:genetics
D002518:Ceramides; D011500:Protein Synthesis Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D003474:Curcumin