cyclin-d1 and ajoene

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.

Topics: Antineoplastic Agents; Apoptosis; beta Catenin; Casein Kinase Ialpha; Cell Line; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Cyclin D1; Disulfides; Garlic; HEK293 Cells; Humans; Phosphorylation; Sulfoxides; Wnt Signaling Pathway