Dataset Information

Z-Ajoene Inhibits Growth of Colon Cancer by Promotion of CK1α Dependent β-Catenin Phosphorylation.

ABSTRACT: Aberrant activation of a Wnt/β-catenin pathway results in nuclear accumulation of β-catenin in colon cancer. Inhibiting β-catenin is one strategy for treating colon cancer. Here, we identified Z-ajoene, a sulfur containing compound isolated from crushed garlic, as an inhibitor of colon cancer cell growth. Z-Ajoene repressed β-catenin response transcriptional activity, intracellular β-catenin levels, and its representative target protein levels (c-Myc and cyclin D1) in SW480 colon cancer cells. To clarify the regulatory mechanism of decreased β-catenin levels, we examined the effect of Z-ajoene on β-catenin phosphorylation, which is involved in β-catenin degradation. Z-Ajoene promoted the phosphorylation of β-catenin at Ser45 in a casein kinase 1α (CK1α)-dependent manner, which is an essential step in β-catenin degradation in the cytosol. These findings indicate that Z-ajoene from garlic may be a potential chemotherapeutic agent by modulating CK1α activity and the Wnt/β-catenin signaling pathway.

SUBMITTER: Li H

PROVIDER: S-EPMC7037095 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Z-Ajoene Inhibits Growth of Colon Cancer by Promotion of CK1α Dependent β-Catenin Phosphorylation.

Li Hua H Jeong Ji Hye JH Kwon Sung Won SW Lee Sang Kook SK Lee Hwa Jin HJ Ryu Jae-Ha JH

Molecules (Basel, Switzerland) 20200206 3

Aberrant activation of a Wnt/β-catenin pathway results in nuclear accumulation of β-catenin in colon cancer. Inhibiting β-catenin is one strategy for treating colon cancer. Here, we identified Z-ajoene, a sulfur containing compound isolated from crushed garlic, as an inhibitor of colon cancer cell growth. Z-Ajoene repressed β-catenin response transcriptional activity, intracellular β-catenin levels, and its representative target protein levels (c-Myc and cyclin D1) in SW480 colon cancer cells. T ...[more]

PMID: 32041324

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Project description:Although mutations in Kras are present in 21% of lung tumors, there is a high level of heterogeneity in phenotype and outcomes amongst lung cancer patients suggesting the importance of other pathways. Wnt/β-catenin signaling is a known oncogenic pathway that plays a well defined role in colon and skin cancer but its role in lung cancer remains unclear. We show that activation of Wnt/β-catenin in the bronchiolar epithelium of the adult lung does not promote tumor development by itself. However, activation of Wnt/β- catenin signaling leads to a dramatic increase in tumor formation both in overall tumor number and size compared to KrasG12D alone. We show that activation of Wnt/β- catenin signaling significantly alters the KrasG12D tumor phenotype resulting in a phenotypic switch from bronchiolar epithelium to the highly proliferative distal progenitors found in the embryonic lung. This is associated with a decrease in E- cadherin expression at the cell surface which may increase metastasis in Wnt/β-catenin signaling positive tumors. Together, these data suggest that activation of Wnt/β-catenin signaling in combination with other oncogenic pathways in lung epithelium may lead to a more aggressive phenotype due to the imposition of an embryonic distal progenitor phenotype accompanied by decreased E-cadherin expression. We performed microarray analysis of control murine lung, CC10-cre:KrasG12D, and CC10-cre:Ctnnb1ex3flox:LSL-KrasG12D double mutant micro-dissected murine lung tumors to determine their transcriptional phenotype. Lungs of five-month-old mice were PBS inflated and all the tumors in each lobe were dissected. The total number of tumors obtained from three out of the 5 pulmonar lobes of each animal was called a sample the other two lobes were saved in case there were problems and the array needed to be repeated. Trizol was used to isolate RNA for microarray analysis. Samples & Genotypes: control murine lung n=2 animals, CC10-cre:KrasG12D n=2 animals, and CC10-cre:Ctnnb1ex3flox:LSL-KrasG12D n=2 animals.

Dataset Information

Z-Ajoene Inhibits Growth of Colon Cancer by Promotion of CK1α Dependent β-Catenin Phosphorylation.

Publications

Z-Ajoene Inhibits Growth of Colon Cancer by Promotion of CK1α Dependent β-Catenin Phosphorylation.

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