Abstract
Background: Nano-based drug delivery systems have shown several advantages in cancer treatment like specific targeting of cancer cells, good pharmacokinetics, and lesser adverse effects. Liver cancer is a fifth most common cancer and third leading cause of cancer-related mortalities worldwide.
Objective: The present study focusses to formulate the selenium (S)/chitosan (C)/polyethylene glycol (Pg)/allyl isothiocyanate (AI) nanocomposites (SCPg-AI-NCs) and assess its therapeutic properties against the diethylnitrosamine (DEN)-induced liver cancer in rats via inhibition of oxidative stress and tumor markers.
Methodology: The SCPg-AI-NCs were synthesized by ionic gelation technique and characterized by various characterization techniques. The liver cancer was induced to the rats by injecting a DEN (200 mg/kg) on the 8th day of experiment. Then DEN-induced rats treated with 10 mg/kg of formulated SCPg-AI-NCs an hour before DEN administration for 16 weeks. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) content, albumin, globulin, and total protein were examined by standard methods. The level of glutathione (GSH), vitamin-C & -E, and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities were examined using assay kits. The liver marker enzymes i.e., alanine transaminase (ALT), aspartate tansaminase (AST), gamma-glutamyl transaminase (GGT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) activities, alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA), Bax, and Bcl-2 levels, and caspase-3&9 activities was examined using assay kits and the liver histopathology was assessed microscopically by hematoxylin and eosin staining method. The effect of formulated SCPg-AI-NCs on the viability and apoptotic cell death on the HepG2 cells were examined using MTT and dual staining assays, respectively.
Results: The results of different characterization studies demonstrated the formation of SCPg-AI-NCs with tetragonal shape, narrowed distribution, and size ranging from 390 to 450 nm. The formulated SCPg-AINCs treated liver cancer rats indicated the reduced levels of 8-OHdG, albumin, globulin, and total protein. The SCPg-AI-NCs treatment appreciably improved the GSH, vitamin-C & -E contents, and SOD, CAT, GPx, and GR activities in the serum of liver cancer rats. The SCPg-AI-NCs treatment remarkably reduced the liver marker enzyme activities in the DEN-induced rats. The SCPg-AI-NCs treatment decreased the AFP and CEA contents and enhanced the Bax and caspase 3&9 activities in the DEN-induced rats. The SCPg-AI-NCs effectively decreased the cell viability and induced apoptosis in the HepG2 cells.
Conclusion: The present findings suggested that the formulated SCPg-AI-NCs remarkably inhibited the DEN-induced liver carcinogenesis in rats. These findings provide an evidence that SCPg-AI-NCs can be a promising anticancer nano-drug in the future to treat the liver carcinogenesis. (C) 2022 The Authors. Published by Elsevier B.V. on behalf of King Saud University.