TY - JOUR
T1 - Novel curcumin analogs, GO-Y030 and GO-Y078, are multitargeted agents with enhanced abilities for multiple myeloma
AU - Kudo, Chieko
AU - Yamakoshi, Hiroyuki
AU - Sato, Atsuko
AU - Ohori, Hisatsugu
AU - Ishioka, Chikashi
AU - Iwabuchi, Yoshiharu
AU - Shibata, Hiroyuki
PY - 2011/11
Y1 - 2011/11
N2 - 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 (PBK)I/KT, Janus kinase (JAK)lsignal transducer and activator of transcription 3 (STAT3), and interferon regulatory factor 4 (1RF4) pathways, is a major reason for treatment failure. Curcumin can regulate these molecules, but its low bioavailability prevents its clinical application. Materials and 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. Conclusion: GO-Y030 and GO-Y078 are potential therapeutic candidates with enhanced abilities for multiple myeloma.
AB - 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 (PBK)I/KT, Janus kinase (JAK)lsignal transducer and activator of transcription 3 (STAT3), and interferon regulatory factor 4 (1RF4) pathways, is a major reason for treatment failure. Curcumin can regulate these molecules, but its low bioavailability prevents its clinical application. Materials and 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. Conclusion: GO-Y030 and GO-Y078 are potential therapeutic candidates with enhanced abilities for multiple myeloma.
KW - Curcumin analog
KW - IRF4
KW - JAK/STAT3
KW - Multiple myeloma
KW - NF-κB
KW - PI3K/AKT
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M3 - Article
C2 - 22110192
AN - SCOPUS:83055191355
VL - 31
SP - 3719
EP - 3726
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 11
ER -