Apoptotic and antioxidant activities of extracts of Spondias monbin stem bark in dimethylhydrazine (DMH)-induced colorectal carcinogenesis in Wistar rats

Abstract

Background: Colorectal cancer is the third most prevalent malignant neoplasm in the world and remains a leading cause of death, particularly in western nations. This study aimed to evaluate the apoptotic and antioxidant activities of Spondias mombin stem bark extracts in dimethylhydrazine (DMH) induced colon cancer in Wistar rats as well as to investigate the binding affinities of epicatechin, kaempferol and Lunamarin against p53 and caspase 3 proteins. Methods: A total of thirty-five (35) male Wistar rats were used for this experiment. They were grouped into five groups: Group 1 (normal control), Group 2 (DMH only- negative control), Group 3 (DMH + Xeloda - Standard Drug), Group 4 (DMH + 500 mg/kg bwt crude hydroethanol extracts), Group 5 (DMH + 500 mg bwt crude ethanol extracts. Results: The results showed high expression of proapoptotic genes which are Caspase-3 genes, B cell lymphoma 2 genes, and p53 genes and there was down regulation of antiapoptotic genes - Bcl like protein 4 genes. Also, the extracts of S. mombin stem bark attenuate the decreased antioxidant status (CAT, SOD and GSH) of DMN-induced colorectal cancer in rats and a significant decrease in the malondialdehyde levels. Molecular docking of the compounds (epicatechin, kaempferol and Lunamarin) against caspase 3 proteins possesses strong binding affinities with binding energies of -7.1, -7.0 and -7.5 kcal/mol respectively. However, kaempferol had similar binding energy(-7.0 kcal/mol) when docked against p53 gene. Conclusion: Therefore, from the study, it was concluded that Spondias mombin stem bark has apoptotic and antioxidant properties.

Keywords

• Apoptosis
• Spondias mombin
• Tumor suppressive gene
• Colon carcinogenesis