In Vitro: ICG-001 (5μM) inhibits leptin-induced EMT, invasion and tumorsphere formation in MCF7 cells.?ICG-001 can phenotypically rescue normal nerve growth factor (NGF)-induced neuronal differentiation and neurite outgrowth in the presenilin-1 mutant cells, emphasizing the importance of the TCF/β-catenin signaling pathway on neurite outgrowth and neuronal differentiation. ICG-001 (25μM) treatment reduces the steady-state levels of Survivin and Cyclin D1 RNA and protein in SW480 cells, both of which can be up-regulated by β-catenin. ICG-001 selectively induces apoptosis in transformed cells but not in normal colon cells, and reduces in vitro growth of colon carcinoma cells.
In Vivo: ICG-001 (5 mg/kg per day) significantly inhibits beta-catenin signaling in mice, while concurrently preserving the epithelium.?Administration of a water-soluble analog of ICG-001 for 9 weeks reduces the formation of colon and small intestinal polyps by 42% as effectively as the nonsteroidal antiinflammatory agent MK-231, which has consistently demonstrated efficacy in this model. ICG-001 (150 mg/kg, i.v.) demonstrates a dramatic reduction in tumor volume over the 19-day course of treatment, with no mortality or weight loss in the SW620 nude mouse xenograft model of tumor regression.