Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

The present study aimed to investigate the efficacy of Punica granatum L. extract and Ginkgo biloba on colon cancer- induced in male albino rats. For induction of colon cancer, rats were intrarectally administered with N-methylnitrosourea (MNU). Animals were intraperitoneally injected with 5-fluorouracil or treated orally with Punica granatum L. extract (2.25 or 4.5 g/kg b.wt.) or Ginkgo biloba (0.675 or 1.35 g/kg b.wt.). Cancer group declared a significant upregulation in the gene expression of Ý-catenin, K-ras and C-myc in colon tissue. Furthermore, a significant increase in colon protein expression of COX-2, cyclin D1, and survivin; this was associated with a significant elevation in the circulating levels of all studied biochemical markers (CEA, CCSA-4, MMP-7, TGF-Ý, EGF, and Bcl-2). Additionally, histopathological investigation of colon tissue sections showed dysplasia and anaplasia in the lining epithelial cells of the glandular structure. On the contrary, treatment of tumor bearing rats with the standard drug 5-fluorouracil, as well as the natural tested agents; viz., Punica granatum L. extract and Ginkgo biloba, showed a significant downregulation in the gene expression of Ý-Catenin, K-ras and C-myc. Additionally, all treated groups exhibited a marked decrease in the protein expression of COX-2, cyclin D1, and survivin in colon tissue; this was accompanied by a significant reduction in the circulating levels of all the studied biomarkers. Improved biomarkers were reflected on the marked recovery of the histological structure. From the present results, it could be concluded that the selected medicinal plants possess a promising therapeutic role against induced colon cancer through their anti-inflammatory, anti-proliferative and apoptotic potentials with the involvement of Wnt/Ý-catenin, Ras and TGF-Ý signaling

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