Effectiveness of theobromine on inhibition of 1,2-dimethylhydrazine-induced rat colon cancer by suppression of the Akt/GSK3β/β-catenin signaling pathway

[Display omitted] •Theobromine, at both doses, prevented the formation of cancerous and precancerous lesions.•Theobromine, at both doses, enhanced the immunostaining of APC tumor suppressor.•Theobromine, at both doses, reduced the activation of Akt and expression of p-GSK3β and cyclin D1.•200 mg/kg of theobromine reduced the mRNA and protein expression of β-catenin. This study aimed to investigate the effect of theobromine on dimethylhydrazine (DMH)-induced colon cancer. Male Wistar rats were divided into four groups and injected with saline (negative control) or 30 mg/kg DMH (other three groups) two times a week for 12 weeks. The negative control and DMH-treated control rats were treated with water and the other two groups with theobromine, at the dose of 100 or 200 mg/kg, two weeks before and during the period of injection. Both doses of theobromine reduced the volume and number of tumors, the number of aberrant crypts, and the expression of p-Akt, p-GSk3β, and cyclinD1, and also increased the expression of APC tumor suppressor. A significant reduction in the expression of β-catenin was observed in the rats treated with the high dose of theobromine. The results indicated that theobromine may be an effective chemopreventive agent for colon cancer by inhibition of the Akt/GSk3β/β-catenin pathway.