Another study by Ruan et al. in KM12C colon cancer cells showed that berberine promoted the interaction of receptor retinoid X receptor alpha (RXRα) with nuclear β-catenin, leading to c-Cbl-mediated degradation of β-catenin, thereby inhibiting the proliferation of colon cancer cells, which was attributed to the direct binding of berberine with a unique region comprising residues Gln275, Arg316 and Arg371 in nuclear RXRα [145], indicating berberine as an RXRα activator. Here, CBL is linked to colonic neoplasm.