Myo-inositol reduces β-catenin activation in colitis

AIM To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate p beta-catenin(S552) as a biomarker of recurrent dysplasia. METHODS We examined the effects of dietary myo-inositol treatment on inflammation, p beta-catenin(S552) and pAkt levels by histology and western blot in IL-10(-/-) and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear p beta-catenin(S552) in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia. RESULTS In mice, p beta-catenin(S552) staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia (LGD), two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans, p beta-catenin(S552) staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease. CONCLUSION Enumerating crypts with increased numbers of p beta-catenin(S552) - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.