title: Novel curcumin analogs, GO-Y030 and GO-Y078, are multi-targeted agents with enhanced abilities for multiple myeloma.
abstract: BACKGROUND
  Multiple myeloma remains an incurable malignancy despite of the recent approval of new molecular-targeted agents. The complex molecular mechanism, composed of various signal networks, including nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PI3K)/AKT, Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), and interferon regulatory factor 4 (IRF4) pathways, is a major reason for treatment failure. Curcumin can regulate these molecules, but its low bioavailability prevents its clinical application.
  
  
  METHODS
  Growth-suppressive abilities of newly synthesized analogs, GO-Y030 and GO-Y078 were analyzed. Molecular-targeted abilities of the analogs for NF-κB, PI3K/AKT, JAK/STAT3, IRF4 pathways, as well as inhibition of interleukin-6 (IL-6) production, were also examined.
  
  
  RESULTS
  GO-Y030 and GO-Y078 were 7 to 12-fold more potent growth suppressors for myeloma cells, and 6- to 15-fold stronger inhibitors of NF-κB, PI3K/AKT, JAK/STAT3, and IRF4 pathways than curcumin. GO-Y78 also 14-fold more potently inhibited IL-6 production.
  
  
  CONCLUSIONS
  GO-Y030 and GO-Y078 are potential therapeutic candidates with enhanced abilities for multiple myeloma.
authors: Department of Clinical Oncology, Faculty of Medicine, Akita University, Hondo1-1-1, Akita, Japan.
authors: Chieko
authors: C
authors: Kudo
authors: Hiroyuki
authors: H
authors: Yamakoshi
authors: Atsuko
authors: A
authors: Sato
authors: Hisatsugu
authors: H
authors: Ohori
authors: Chikashi
authors: C
authors: Ishioka
authors: Yoshiharu
authors: Y
authors: Iwabuchi
authors: Hiroyuki
authors: H
authors: Shibata
mesh_terms: D017209:Apoptosis; D001555:Benzene Derivatives / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D000099218:Interferon Regulatory Factor-4
chemical_list: D001555:Benzene Derivatives; D003474:Curcumin; D050835:Interferon Regulatory Factors; D015850:Interleukin-6; D053613:Janus Kinase 1; D007659:Ketones; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D000099218:Interferon Regulatory Factor-4; C541015:1,5-bis(3,5-bis(methoxymethoxy)phenyl)penta-1,4-dien-3-one; C494086:STAT3 protein, human; C507904:JAK1 protein, human