Protective effect of eugenol and glycyrrhizic acid on experimental colorectal cancer model

Cancer is the leading cause of death in humans. Colorectal cancer (CRC), the 4th most common cancer type among all cancers both in men and women, ranks as the 3rd among all cancer deaths. It is estimated that nearly one million people are diagnosed with CRC worldwide annually. The antineoplastics used for the treatment of cancer have severe side effects. The aim of this study was to investigate the potential chemopreventive effects of eugenol (EU) and glycyrrhizic acid (GA) on azoxymethane (AOM)-induced colorectal cancer in rats. In the study, 80 Sprague Dawley male rats were used. The rats were randomly divided into eight groups as follows: Control, AOM (15mg/kg bw., sc, once a week for two weeks), EU (EU 100 mg/kg bw., gavage), GA (GA 15 mg/kg bw., gavage), EU+GA, AOM+EU, AOM+GA, and AOM+EU+GA. All the rats except those in the control and AOM groups were treated with EU and GA for 16 weeks. At the end of the study, the colon tissues were examined in terms of Aberrant Crypt Foci (ACF) and histopathology. Malondialdehyde (MDA) and reduced glutathion (GSH) levels as well as superoxide dismutase (SOD) and catalase (CAT) activities were evaluated biochemically in both tissue and blood samples. In addition, Bax, Bcl-2, COX-2, NF-kB and p53 protein expressions in colon samples were determined by Western blotting. In the colon tissues of rats treated with AOM, MDA levels and CAT activities were found out to increase, whereas GSH levels and SOD activities decreased. On the other hand, no significant changes were observed in the oxidative stress parameteres of blood samples. AOM treatment increased Bcl-2/Bax ratio but downregulated NF-kB, COX-2, p53 and Bax expressions. In the histopathological examination, an increase was detected in ACF numbers and malignant tumoral lessions. The use of EU and EU+GA decreased oxidative stress and ACF numbers, induced apoptosis, and upregulated p53 expression in azoxymethane-treated rats. In conclusion, EU and EU+GA were determined to be effective against colorectal cancer when compared with the other treatment groups. Keywords: Rat, eugenol, glycyrrhizic acid, azoxymethane, ACF, oxidative stress.