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Purpose: To examine the chemopreventive activity of curcumin analogues, hexagamavunone-0 (HGV- 0) and gamavutone-0 (GVT-0), compared to curcumin in a colorectal cancer model in Wistar rats.
Methods: Rats (n = 25) were assigned to one of five groups (n = 5 in each group). Colorectal cancer was induced in the control group with subcutaneous injection of 1,2-dimethylhydrazine (DMH) 60 mg/kg once a week for 15 weeks. In addition to DMH injection, treatment groups were treated with curcumin (20, 40, or 80 mg/kg), gamavutone-0 (GVT-0; 20, 40, or 80 mg/kg), and hexagamavunone (HGV-0; 20, 40, or 80 mg/kg) orally twice a week for 15 weeks. The number and volume of nodules in the colorectal area were observed after laparatomy. Histopathological analysis was performed using H & E staining and immunohistochemistry with antibodies against adenomatous polyposis coli (APC) and cyclooxygenase 2 (COX-2).
Results: All treatments reduced colorectal nodule volume, but only HGV-0 significantly decreased the numbers of nodules compared to DMH controls (p < 0.05). The reduction was 96.1 % with 40 mg/kg HGV-0. Mutated APC expression was inhibited by curcumin, GVT-0, and HGV-0 at a dose of 40 mg/kg, whereas COX-2 expression was mostly inhibited by HGV-0 (20 and 40 mg/kg) and curcumin to a lesser extent, but not inhibited by GVT-0 treatment in rat colorectal cancer.
Conclusion: HGV-0 showed superior chemoprevention compared to GVT-0 and curcumin. HGV-0 at a dose of 40 mg/kg significantly reduced the number and volume of colorectal nodules. The mechanism of chemoprevention of HGV-0 is related to its inhibition of APC mutation and COX-2 expression.
Keywords: Curcumin, Gamavutone-0, Hexagamavunone-0, Colorectal cancer, Adenomatous polyposis coli, Cyclooxygenase-2