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. 2017 Jan 12:23:163-171.
doi: 10.12659/msm.902711.

Curcumin Inhibits Gastric Carcinoma Cell Growth and Induces Apoptosis by Suppressing the Wnt/β-Catenin Signaling Pathway

Affiliations

Curcumin Inhibits Gastric Carcinoma Cell Growth and Induces Apoptosis by Suppressing the Wnt/β-Catenin Signaling Pathway

Ruzhen Zheng et al. Med Sci Monit. .

Abstract

BACKGROUND Curcumin has well-known, explicit biological anti-tumor properties. The Wnt/β-catenin signaling pathway plays a central role in tumor cell proliferation and curcumin can regulate the Wnt/b-catenin signaling pathway of several carcinomas. The aim of this study was to investigate the impact of curcumin on the Wnt/β-catenin signaling pathway in human gastric cancer cells. MATERIAL AND METHODS We used 3 gastric cancer cell lines: SNU-1, SNU-5, and AGS. Research methods used were MTT assay, flow cytometry, clonogenic assay, annexin V/PI method, Western blotting analysis, tumor formation assay, and in vivo in the TUNEL assay. RESULTS Curcumin markedly impaired tumor cell viability and induced apoptosis in vitro. Curcumin significantly suppressed the levels of Wnt3a, LRP6, phospho-LRP6, β-catenin, phospho-β-catenin, C-myc, and survivin. Xenograft growth in vivo was inhibited and the target genes of Wnt/β-catenin signaling were also reduced by curcumin treatment. CONCLUSIONS Curcumin exerts anti-proliferative and pro-apoptotic effect in gastric cancer cells and in a xenograft model. Inhibition of the Wnt/β-catenin signaling pathway and the subsequently reduced expression of Wnt target genes show potential as a newly-identified molecular mechanism of curcumin treatment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Anti-proliferative activity of curcumin on gastric cancer cell lines. Curcumin significantly reduced the cell viability of SNU-1, SNU-5, and AGS cells in dose- and time-dependent manners.
Figure 2
Figure 2
Colony formation of SNU-1, SNU-5, and AGS cells were decreased in a dose-dependent manner after curcumin treatment.
Figure 3
Figure 3
Curcumin induced apoptosis of SNU-1, SNU-5, and AGS cells in a dose-dependent manner.
Figure 4
Figure 4
Curcumin decreased protein levels of the Wnt/β-catenin signaling pathway on SNU-1, SNU-5, and AGS cells in a dose-dependent manner. The expressions of Wnt3a, LRP6, phospho-LRP6 at Ser1490, β-catenin, phospho-β-catenin at Ser675, C-myc, and survivin were decreased in a dose-dependent manner after curcumin treatment.
Figure 5
Figure 5
The anti-tumor effects of curcumin on tumor growth of xenograft model of AGS cells. Tumor volumes and weight of curcumin group reduced significantly in the model mice. * Statistically significant difference (P<0.01) compared to the control group.
Figure 6
Figure 6
The effect of curcumin on apoptosis in tumor tissues. The apoptosis index significantly increased after curcumin treatment. *Statistically significant difference (P<0.01) compared to the control group.
Figure 7
Figure 7
The effect of curcumin on Wnt/β-catenin signaling pathway protein expressions in tumor tissues. Western blotting analysis for Wnt3a, LRP6, phospho-LRP6 at Ser1490, β-catenin, phospho-β-catenin at Ser675, C-myc, and survivin proteins from AGS xenografts.

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