Azadirachta indica Leaf Extract Mediated Green Synthesized Vanadium Nanoparticles Exhibit Potent Anticancer Activity against Hepatocellular Carcinoma in Hep3B Cells and in vivo, Compared with Sorafenib and Combination Treatment
摘要
To overcome the drawbacks of conventional therapies and drug resistance in hepatocellular carcinoma (HCC), we employed green synthesized vanadium nanoparticles (GVNPs) to treat HCC in vitro and in vivo. In vitro anticancer effect of GVNPs was assessed by cell viability assay, multiple fluorescence staining to detect cell death against Hep3B cells. The IC50 value of the GVNPs was 5 µg/mL i.e. even lower than the standard drug sorafenib. DNA damage study was performed through agarose gel electrophoresis and comet assay; it was observed that GVNPs induce both single and double-stranded DNA breaks. Further, increased oxidative stress and alterations in mitochondrial membrane potential could be one of the modes of action of GVNPs anticancer effect. Encouraging outcomes from in vitro studies legitimate us to explore the potential of GVNPs in vivo using Sprague–Dawley rats. The GVNPs were found to reduce HCC, marked by a significant decrease in the activities of ALT, AST and ALP in serum. As observed through liver histology, combination of GVNPs plus sorafenib treatment did not display encouraging results when compared to GVNPs alone treated animals. Additionally, Masson’s staining and α-smooth muscle actin expression through Western blot analysis disclosed reduced collagen deposition in GVNPs treated rat liver than that of HCC control animals, portraying GVNPs treated rat liver recurring to healthy condition. The data obtained provide compelling evidence for the utility of GVNPs as emerging therapeutics in HCC treatment paving the road towards clinical investigations.