الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
Liver cancer is one of the leading causes of cancer-related mortality. Ruthenium complexes represent a new promising family of metal-based anticancer complexes. A novel ruthenium(III)-pyrimidine Schiff base complex (RuL) was synthesized and characterized. In vitro antimicrobial activities of the synthesized ruthenium complexes against different microbial strains were screened. Cytotoxicity of the complex was screened against breast cancer (MCF-7 and T47D), cancer colorectal (HCT116), hepatocellular (HepG2) cell lines as well as normal human splenic fibroblasts cell lines (HSF). The complex effectively inhibited the tested cancer cells with variable degrees, with the highest activity towards HepG2 and high selectivity between HepG2 and normal HSF cells. The complex induced apoptosis and cell cycle arrest in the S phase of HepG2 cells. It significantly induced the expression of H2AX, caspase 3 and 7 genes with increased protein level of caspase 3. RuL inhibited VEGF-A, and mTOR /AKT, SND1, NFkB gene expression. The molecular docking studies supported the apoptotic effect of the complex against HepG2 cells probably due to strong interaction of the complex with DNA. Also, the possible binding interaction of the complex with caspase 3 could be responsible for elevated activity of caspase 3 treated cells. Based on the in vitro results, the hepatoprotective activity of RuL was screened against DEN + CCl4 induced liver toxicity in rats. Serum liver, kidney, and lipid biomarkers, haematological profile, antioxidants enzymes and serum AFP were assessed. Histopathological
evaluation, macroscopic and microscopic characterizations and immunohistochemistry analysis were also performed to authenticate the outcomes of the present work. The RuL complex successfully improved all the tested biomarkers and diminished the level of the tumor marker (AFP). Histopathological features showed recovery of a hepatic architecture in rats bearing HCC and improved immunohistochemistry results. The results of both in vitro and in vivo studies indicated that RuL could be a potential anticancer candidate.