Combination Therapy with Quercetin and 5-Fluorouracil Ameliorates 1,2-Dimethylhydrazine Induced Carcinogenesis in the Colon of Wistar Rats. | ||||
| Bulletin of Egyptian Society for Physiological Sciences | ||||
| Article 11, Volume 37, Issue 2, December 2017, Page 227-244 PDF (899.91 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/besps.2017.8276 | ||||
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| Authors | ||||
Bakheet E. M. Elsadek1; Mohamed A. Abdel Aziz1; Sahar E. M. El-Deek  2; Mohamed M. M. Mahdy1; Mahmoud R. Hussein3
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| 1Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, P.O. Box No. 71524 Assiut, Egypt. | ||||
| 2Department of Medical Biochemistry, Faculty of Medicine, Assiut University, P.O. Box No. 71526, Assiut, Egypt. | ||||
| 3Department of Pathology, Faculty of Medicine, Assiut University, P.O. Box No. 71526, Assiut, Egypt. | ||||
| Abstract | ||||
| Background: Colorectal carcinoma (CRC) is a common cause of cancer-related death worldwide. 5-fluorouracil (5-FU), a first-line chemotherapeutic drug in CRC, has several side effects limiting its therapeutic outcomes. Quercetin (QU) is a dietary bioflavonoid with antioxidant and cytotoxic prooxidant properties. Here, we hypothesize that combination treatment with QU and 5-FU can modulate 1,2-dimethylhydrazine (DMH) induced histological and biochemical changes in the colon of Wistar rats. Methods: A Wistar rats CRC model was established and the animals were randomly divided into five groups. Rats in group A received a suspending vehicle. Group B rats received DMH twice a week subcutaneously for 4 weeks. Animals in the other groups (C, D and E) received the same treatment of DMH, along with QU or 5-FU (individually) or combined QU+5-FU treatment. Results: The DMH-treated rats developed adverse histological alterations (aberrant crypt foci, ACF) and biochemical changes (elevated serum CA19-9; reduced tissue levels of enzymatic antioxidants; elevated CDH12 protein expression and decreased SOX7 mRNA levels). Treatment of DMH-treated animals with QU+5-FU (but not with QU or 5-FU, individually) significantly reversed these changes (i.e., suppressed the formation of ACF; decreased the CA19-9 levels; reduced CDH12 protein expression and increased SOX7 mRNA expression). Conclusions: Conclusively, to the best of our knowledge, our study was the first to evaluate the effects of QU+5-FU treatment on the histological and molecular changes following DMH administration in a rat colon model. Our data suggest that combination therapy with QU+5-FU has therapeutic benefits in colon cancer induced by DMH, with potential for translation to spontaneous disease. | ||||
| Keywords | ||||
| 5-Fluorouracil; CDH12; Colorectal carcinoma Dimethylhydrazine; Quercetin; SOX7 | ||||
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