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-11th to one-14th 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.