W346 inhibits cell growth, invasion, induces cycle arrest and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway
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The therapeutic agent selectively killing cancer cells is urgently needed for gastric cancer treatment. Curcumin has been investigated for its effect on the cancer treatment because of its significant therapeutic potential and safety profile. A synthetic unsymmetry mono-carbonyl compound termed W346 was developed from curcumin. In this study, we investigated the potential antineoplastic effect and mechanism of W346 against human gastric cancer cells. W346 suppressed the proliferation and invasion, blocked cell cycle arrest at G2/M phase, and increased apoptosis in gastric cancer cells, and it presented obviously improved anticancer activity than curcumin. Moreover, W346 effectively inhibited tumor necrosis factor (TNF-α)-induced NF-κB activation by suppressing IKK phosphorylation, inhibiting IκB-α degradation, and restraining the accumulation of NF-κB subunit p65 nuclear translocation. W346 also affected NF-κB-regulated downstream products involved in cycle arrest and apoptosis. In a word, W346 exhibited significantly improved anti-gastric cancer activity over curcumin by targeting NF-κB signaling pathway, and it is likely to be a promising starting point for the development of curcumin-based therapeutic agent.
KeywordsW346 Anticancer drug Curcumin Gastric cancer Apoptosis NF-κB
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Conflicts of interest
This work was supported by the National Natural Science Foundation of China (Grant No. 81272462), the Zhejiang Province Natural Science Fund of China (Grant Nos. LY14H160044, Y13H300005), and the Technology Foundation for Medical Science of Zhejiang Province (Grant No. 2012KYA129).
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