In vitro and in vivo studies of a newly synthesized copper-cetyl tri-methyl ammonium bromide combined with gallium oxide nanoparticles complex as an antitumor agent against hepatocellular carcinoma

Abstract

Objective: Hepatocellular carcinoma (HCC) is one of the most leading causes of death worldwide. Previous studies reported that gallium alone and cetyltrimethylammonium bromide (CTAB) have antineoplastic activities; therefore, this study aimed to evaluate the activity of copper‐cetyl tri‐methyl ammonium bromide with gallium oxide nanoparticles (Cu‐CTAB+GaO‐NPs) against HCC by using in vitro and in vivo studies. Methods: In vitro study was performed to evaluate the cytotoxic effects of Cu‐CTAB+GaO‐NPs and GaO‐NPs on HepG‐2 cell line using crystal violet dye assay. In vivo study was done on diethyl nitrosamine (DEN) induced HCC Wister rats. Rats were randomly divided into eight groups; control, Cu‐CTAB, GaO‐NPs, Cu‐CTAB+GaONPs, DEN, DEN+Cu‐CTAB, DEN+GaO‐NPs and DEN+Cu‐CTAB+GaO‐NPs. Histopathological examination of liver and biochemical parameters such as liver function markers, oxidative stress-antioxidants markers, tumor makers, apoptosis makers were studied. Results: Results obtained from in vitro study revealed that Cu‐CTAB+GaO‐NPs and GaO‐NPs affect the cell viability of HepG‐2 cancer cell with IC50 0.2 μg/ml and 360 μg/ml, respectively. Cu‐CTAB+GaO‐NPs exerted an antiproliferative effect in experimental rat models of HCC, as demonstrated both histologically, since it facilitated the tissue recovery of the damaged liver, and biochemically as showed by the reduction of liver function markers (ALT & AST), oxidative stress markers (MDA) and tumor makers (AFP,TGF‐β1,α‐L–Fucosidase); while antioxidants markers (SOD), apoptosis markers (caspase‐3 mRNA) and araginase activity were elevated in DEN+Cu‐CTAB, DEN+GaO‐NPs and DEN+Cu‐CTAB+GaO‐NPs groups when compared to DEN group. Conclusion: The present study demonstrated that both Cu‐CTAB alone and/or combined with GaO‐NPs exerted cytotoxic effects against DEN-induced HCC, which would in turn, speculate a possible therapeutic role of the novel Cu‐CTAB+GaO‐NPs compound.