Nabag (Zizyphus spina-christi) Extract Prevents Aberrant Crypt Foci Development in Colons of Azoxymethane-Treated Rats by Abrogating Oxidative Stress and inducing Apoptosis

Nejib Guizani,Mohammad Shafiur Rahman,Mostafa Ibrahim Waly,Vandita Singh

doi:10.7314/apjcp.2013.14.9.5031

Abstract

Zizyphus spina-christi (ZSC) fruit is a rich source of bioactive compounds but any medicinal properties in chemoprevention of colon cancer have hitherto not been studied. The aim of the present study was to examine in vivo protective effects of ZSC water extract on colon carcinogenesis in azoxymethane (AOM)-treated rats. Our results showed that ZSC significantly reduced AOM-induced colonic aberrant crypt foci development and AOM-induced oxidative stress as indicated by restoration of endogenous glutathione depletion and abrogating the impairment of total antioxidant capacity. Caspase-3 cleavage, which has been considered as an apoptotic index, was almost undetectable in AOM-treated rats and ZSC exhibited pro-apoptotic effects evidenced by increased levels of cleaved caspase-3. In the studied model, our findings provide the first in vivo evidence that ZSC extract could inhibit the early stage of colon carcinogenesis by preventing oxidative stress and inducing apoptosis.

Highlights

Azoxymethane (AOM) is a specific colon carcinogenic agent that induces the development of aberrant crypt foci in animal models (Hangen and Bennink, 2002; Leonardi et al, 2010)
Our results showed that Zizyphus spina-christi (ZSC) significantly reduced AOM-induced colonic aberrant crypt foci development and AOM-induced oxidative stress as indicated by restoration of endogenous glutathione depletion and abrogating the impairment of total antioxidant capacity
Our findings provide the first in vivo evidence that ZSC extract could inhibit the early stage of colon carcinogenesis by preventing oxidative stress and inducing apoptosis

Summary

Introduction

Azoxymethane (AOM) is a specific colon carcinogenic agent that induces the development of aberrant crypt foci in animal models (Hangen and Bennink, 2002; Leonardi et al, 2010). A recent study has shown that AOM induces oxidative stress in colonic homogenates as it was evident by glutathione (GSH) depletion and impairment of total antioxidant capacity (TAC) (Al-Numair et al, 2011). Colon carcinogenesis is a multistep process, and several lines of evidence proposed that AOM-induced colon cancer development partly by inhibiting the tumor suppressor gene p53-mediated apoptosis and by causing aberrant cell survival, contributed to oncongenesis (Steller, 1995; Arai et al, 1996; Wu et al, 2004). The number of crypts/foci has been shown to increase with time following carcinogenic AOM-treatment, and ACF demonstrate increased colonic cells proliferation (Bird, 1987). The aim of the present study was to investigate the in vivo antiproliferative effect of ZSC extract on colon carcinogenesis and the mechanisms involved

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