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Abstract
This study describes the antiproliferative activity of thiocolchicoside and colchicine compounds in a dose-dependent manner against breast cancer cell line (MCF-7). MTT assay results show that IC50 (inhibitory concentration 50 %) values towards MCF-7 breast cancer cell line were 79.02 and 74.23 nmol for thiocolchicoside and colchicines compounds, respectively. Further, in vitro interaction between thiocolchicoside and colchicine compound ligands binding with the p53 tumor suppressor protein gene and its expression was also confirmed by western blot analysis. Results clearly show that the expression of p53 protein was more abundant in treated MCF-7 cancer cell line and up-regulated expression of the p53 gene was positively correlated with thiocolchicoside and cochicine concentrations used. The thiocolchicoside compound was found to be more effective against p53 protein accumulation levels when compared with colchicine and adriamycin. Molecular docking analysis was performed to reveal the interactions of receptor binding sites (molecular targets) with ligands. These compounds show efficient inhibitory action on the target p53 tumor suppressor protein expression which confirms their increased anti-proliferative activity against cancer cell growth. The present results could be used for the improvement of a novel formulation with enhanced inhibition of MCF-7 cancer cell growth. The docking scores were found to be high in thiocolchicoside compound against cellular tumor antigen p53 (-5.9 kcal/mol) with the strong interaction followed by colchicine (-5.3 kcal/mol) and the hydrogen bond counts, confirming the capability of these compounds for binding with receptor active site. Therefore, thiocolchicoside and colchicine compounds with effective p53 inhibitory activity strongly suggest that these compounds could be used as strong anticancer agents to treat MCF-7 breast cancer cell growth arrest effectively.