Harmol alleviates dimethylhydrazine induced colon cancer by downregulating Bcl2/IL-6/TNF-α expression in association with p53 mediated apoptosis

Objectives: Colorectal cancer is the world's third most prevalent cancer. Herbal drugs are increasingly being used to treat a variety of disorders, including cancer, due to the severe adverse effects. Harmol, natural molecule containing beta-carboline alkaloids, has aroused the interest of researchers due to its diverse biological functions, including anticancer properties. Methods: In this study, the chemotherapeutic effects of harmol have been investigated on HT-29 colon cancer cell line and a rat model of colon cancer. In the in vitro study the cytotoxicity assay, DAPI analysis and the flow cytometric analysis was performed to assess the anticancer efficacy of harmol in HT-29 cell. The colorectal cancer was developed in male Wistar rats through the administration of DMH followed by treatment with DSS. The rats were treated with harmol (100, 200 and 400 mg/kg) for 18 weeks. At the end of therapy, the colon tissues were assessed for ACF, in vivo antioxidant activity, histopathology, immunohistochemistry, immunofluorescence analysis and apoptosis assay. Results: The in vitro data suggested that the harmol therapy would significantly increase the percentage of early apoptosis in HT-29 cells through halting of G0/G1 phase. Furthermore, inhibition of ACF development with improved colonic abrasion and morphological features in colonic mucosal region were noted. Harmol treatment also increased the levels of antioxidants and p53 and downregulated Bcl2, IL-6 and TNF-alpha expression. Conclusion: These outcomes signify that harmol successfully recover colorectal carcinoma by reprogramming the p53, Bcl2, IL-6 and TNF-alpha pathway in rats.