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Tumour Biol. 2016 Apr;37(4):4791-801. doi: 10.1007/s13277-015-4277-2. Epub 2015 Oct 31.

W346 inhibits cell growth, invasion, induces cycle arrest and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway.

Xia Y1,2, Weng B2,3, Wang Z4, Kang Y1,2, Shi L2, Huang G5, Ying S2, Du X1,2, Chen Q1,2, Jin R6,7, Wu J8, Liang G2.

Author information

1
Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
2
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
3
Pharmacy Department, Tonglu First People's Hospital, Hangzhou, Zhejiang, 311500, China.
4
Institute of Sports Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
5
Department of General Surgery, The fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China.
6
Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. jinrongjrjr@163.com.
7
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. jinrongjrjr@163.com.
8
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. wjzwzmu@163.com.

Abstract

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.

KEYWORDS:

Anticancer drug; Apoptosis; Curcumin; Gastric cancer; NF-κB; W346

PMID:
26520440
DOI:
10.1007/s13277-015-4277-2
[Indexed for MEDLINE]

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