| The curcumin analog GO-Y030 is a novel inhibitor of IKKβ that suppresses NF-κB signaling and induces apoptosis. | |
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MedLine Citation:
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PMID: 21272158 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Curcumin is a dietary constituent with tumor-suppressing potential, inhibiting various pathways involved in carcinogenesis. However, because of its low bioavailability, the use of curcumin in in vivo trials has been limited. To overcome this problem, we synthesized more than 50 analogs and identified a monoketone analog, GO-Y030, which has a 30-fold higher potential to suppress tumor cell growth compared with curcumin. We investigated the inhibitory effect of GO-Y030 on NF-κB activation. In thyroid, pancreatic cancers, and cholangiocarcinoma cells, in which NF-κB is activated, NF-κB activation was suppressed to 8-62% of the control value following treatment with 1 μM GO-Y030, an effect comparable to that of 10 μM curcumin. Direct inhibition of IKKβ kinase activity and suppression of nuclear translocation of the NF-κB p65 subunit were observed. The 50% growth inhibition concentrations of GO-Y030 ranged from one-eleventh to one-fourteenth of those of curcumin. GO-Y030 also induced cell death comparable to that induced by curcumin but at a 10-fold lower concentration. In pancreatic and thyroid cancer cells, the growth-inhibitory effect of GO-Y030 was 4- and 15-fold greater, respectively, than that of curcumin. GO-Y030 was a much stronger inducer of apoptosis compared with curcumin. The enhanced potency of GO-Y030 may make it more useful than curcumin, which suffers from low bioavailability. GO-Y030 is a good lead compound for the development of useful compounds for practical cancer chemotherapy. |
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Authors:
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Atsuko Sato; Chieko Kudo; Hiroyuki Yamakoshi; Yoshihiko Uehara; Hisatsugu Ohori; Chikashi Ishioka; Yoshiharu Iwabuchi; Hiroyuki Shibata |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-27 |
Journal Detail:
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Title: Cancer science Volume: - ISSN: 1349-7006 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101168776 Medline TA: Cancer Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2011 Japanese Cancer Association. |
Affiliation:
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Dept. Clinical Oncology, Institute of Development, Aging, and Cancer, Seiryo-cho 4-1, Aoba-ku, Sendai, Miyagi, Japan. Dept. Clinical Oncology, University Hospital, Tohoku University, Seiryo-cho 1-1, Aoba-ku, Sendai, Miyagi, Japan. Dept. Organic Chemistry, Graduate School of Pharmaceutical Science, Aoba 6-3, Aramaki, Aoba-ku, Sendai, Miyagi, Japan. Dept. Cell Biology, Graduate School of Medicine Dept. Clinical Oncology, Faculty of Medicine, Akita University, Hondo1-1-1, Akita 010-0001, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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