Curcumin Inhibits Cell Viability and Increases Apoptosis of SW620 Human Colon Adenocarcinoma Cells via the Caudal Type Homeobox-2 (CDX2)/Wnt/β-Catenin Pathway

Abstract

BackgroundCurcumin is a polyphenol compound extracted from the root of the herb Curcuma longa, which is used in traditional Chinese medicine (TCM). Worldwide, colorectal carcinoma (CRC) is an increasing cause of morbidity and mortality. This study aimed to investigate the effects of increasing concentrations of curcumin on cell viability, proliferation, and apoptosis of SW620 human colonic adenocarcinoma cells cultured in vitro, and the signaling pathways involved.Material/MethodsSW620 human colonic adenocarcinoma cells were cultured in curcumin at concentrations of 0, 4, 8, 16, and 32 μmol/l for 48 hours. Specific small interfering RNA (siRNA) was transfected into SW620 cells to silence the expression of caudal type homeobox-2 (CDX2). Cell viability was measured using the MTT assay. Flow cytometry evaluated cell apoptosis. Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to assess the nuclear translocation of β-catenin and the activation of Wnt signaling.ResultsCurcumin reduced cell viability and increased apoptosis of SW620 human colonic adenocarcinoma cells in a dose-dependent way, and increased the expression of CDX2 but decreased β-catenin nuclear translocation and the expression of Wnt3a, c-Myc, survivin, and cyclin D1. CDX2 silencing significantly reduced the effects of curcumin on SW620 human colonic adenocarcinoma cells. The nuclear translocation of β-catenin, and expression levels of Wnt3a, c-Myc, survivin, and cyclin D1 were significantly higher in CDX2-silenced SW620 cells.ConclusionsCurcumin reduced cell viability and increased apoptosis in SW620 human colonic adenocarcinoma cells by restoring CDX2, which inhibited the Wnt/β-catenin signaling pathway.

Curcumin Suppresses Apoptosis and Inflammation in Hypoxia/Reperfusion-Exposed Neurons via Wnt Signaling Pathway

“…Curcumin was also reported to be a regulator of the Wnt signaling pathway. It was suggested that curcumin plays roles in regulating the Wnt pathway by affecting microRNAs, caudal type homeobox-2 (CDX2), glypican-3, and other molecular targets [29][30][31]. In the present study, we found that in H/Rexposed neurons, curcumin pre-treatment decreased Wnt5a expression, JNK1 phosphorylation, and NF-kB nuclear translocation.…”

Reduced Caudal Type Homeobox 2 (CDX2) Promoter Methylation Is Associated with Curcumin’s Suppressive Effects on Epithelial-Mesenchymal Transition in Colorectal Cancer Cells

“…A previous investigation showed that curcumin suppresses gastric cancer cells through inhibiting the Wnt/β-catenin signaling pathway [ 24 ]. A recent study reported that curcumin inhibits the Wnt/β-catenin pathway by increasing CDX2 expression in CRC cells [ 15 ]. In the present investigation, non-cytotoxic concentrations of curcumin were used to treat SW480 cells to avoid cell death-related gene expression changes.…”

“…Cell viability was assessed by 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay according to the protocol described in previous studies [ 15 ]. SW480 cells, at a density of 1×10 4 cells per well, were treated with curcumin at 0, 0.1, 0.2, 0.4, 0.8, or 1.6 μmol/L for 24 h. An MTT assay kit (Beyotime, Shanghai, China) was used to carry out the assay.…”

Potential Role of Traditional Chinese Medicines by Wnt/β-Catenin Pathway Compared With Targeted Small Molecules in Colorectal Cancer Therapy

“…Curcumin is another inhibitor of ß -catenin in many cancers ( Deguchi, 2015 ). Previous studies illustrated caudal type homeobox-2 (CDX2) is a mediator of the Wnt signaling pathway, and curcumin can reduce cell proliferation and increase apoptosis by restoring CDX2 which inhibited the Wnt/β-catenin signaling pathway ( Jiang X. et al, 2019 ). Besides, curcumin might exert anti-resistant effect of 5-FU on rHCT-116 cells by controlling WNT signal pathway to reverse the EMT progress ( Lu et al, 2020 ).…”