Targeting β-catenin and cytochrome p450 (1B1) by Ellagic Acid in Colon Cancer Cell Lines: Implications for Treatment Applications

Abstract

The knowledge is growing to address ellagic acid (EA) as a promising anti-cancer agent in colon, as well as, other types of human cancers. Up-regulation of β-catenin in colon cancer supports tumorigenic pathways in numerous aspects, which makes the need pressing to target this pathway. Likewise, cytochrome p450 (1B1) sustains carcinogenicity and tumor growth by either; activation of pro-carcinogens, or by inactivation of chemotherapeutic agents. Therefore overexpression of the enzyme has been reported in colon and other types of cancers. The effect of ellagic acid treatment on the level of total and phospho-β-catenin and cytochrome p450 (1B1) was estimated by enzyme-linked immunosorbent assay (ELISA) method in CaCo-2 and HCT-116 colon cancer cells. The influence of ellagic acid on cell proliferation and cell cycle progression was assessed using the CCK-8 kit and flow cytometry analysis, respectively. Results revealed that ellagic acid exhibited an anti-proliferative potential in both cell types, which was associated with increasing number of sub-G1 (apoptotic) cells and cell cycle arrest in G1 phase in ellagic acid-treated cells. This was in harmony with the ability of the drug to increase β-catenin phosphorylation (hence its degradation) and reduce cytochrome 1B1 levels in CaCo-2 and HCT-116 cell lines. These results altogether indicate that different cellular genetics (Ras oncogene and p53 status, in particular) had no impact on the anti-tumor effects of ellagic acid in this model