Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Chemopreventive properties of curcumin analogues, hexagamavunone-0 and gamavutone-0, in rat colorectal cancer model

Risfah Yulianty¹ , Lukman Hakim², Sardjiman ², Gemini Alam¹, Sitarina Widyarini³

¹Pharmacy Faculty, Hasanuddin University, Makassar; ²Pharmacy Faculty, Gadjah Mada University, Yogyakarta; ³Veterinary Faculty, Gadjah Mada University, Yogyakarta, Indonesia.

For correspondence:- Risfah Yulianty Email: risfahyulianty@unhas.ac.id Tel:+6281342506714

Accepted: 9 August 2017 Published: 30 September 2017

Citation: Yulianty R, Hakim L, S, Alam G, Widyarini S. Chemopreventive properties of curcumin analogues, hexagamavunone-0 and gamavutone-0, in rat colorectal cancer model. Trop J Pharm Res 2017; 16(9):2141-2148 doi: 10.4314/tjpr.v16i9.14

© 2017 The authors.
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Abstract

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