MOLECULAR PERSPECTIVES OF MIMOSINE AS A POTENTIAL ANGIOGENIC INHIBITOR IN COLORECTAL CANCER

Abstract

quotObjective: To understand potential of Mimosine (MMS) and its cell inhibitory ability by in silico, in vitro and in vivo evaluations. newlineMethodology: In silico molecular docking study, in vitro analysis, Nuclear staining and apoptotic evaluation were carried out. In vivo tumor dynamics, hematological panel, antioxidant analysis and biochemical evaluations were performed post induction of tumors. The histopathology and iron degeneration in brain and various behavioral parameters were estimated. newlineResults: The in silico study revealed good binding potentials for MMS towards the proteins of the angiogenic cascade. The in vitro analysis provided the cytotoxic potential of the molecule, cellular uptake limits and its DNA fragmentation pattern in HCT-116 cells. The western blotting evaluation demonstrated that MMS exacerbated the expression of HIF-1A and VEGF-A. Apoptotic evaluation revealed considerable apoptosis in HCT-116 cells. In vivo studies revealed a significant reduction in tumor sizes and counts in animals. The RBC and Hb counts were improved while WBC and platelet counts were stabilized. Antioxidant parameters showed improvement in the concentrations of Catalase, SOD and GSH, while MDA levels were suppressed. Biochemical parameters revealed a normalization of their concentrations and the DNA fragmentation pattern was in conjunction to the earlier obtained result in vitro. WB analysis of three angiogenic protens revealed the enhancement and suppression of MMP-9, Ang-2 and PDGF-A respectively. Histopathological analysis revealed the reduction in aggregation of epithelial nuclei while a significant reduction in infiltration of inflammatory cells. newlineConclusion: The current study was designed and conducted with the sole view of determining the potential of MMS to inhibit the markers of the angiogenic cascade. Higher doses of this molecule appeared to exhibit significant efficacy. MMS could possess the ability to enroll in therapeutic strategies of the future for the effective treatment of CRC newlinequot newline