Zinc oxide nanoparticles as a novel anticancer approach; in vitro and in vivo evidence

Abstract

Currently, the outcomes of conventional chemotherapeutic approaches are unsatisfactory. Clinical application of nanoparticles seems promising. We aim to evaluate the possible antitumor activity of zinc oxide nanoparticles (ZnONPs) as a chemotherapeutic approach in in vitro and in vivo experimental models. An in vitro study was performed on three different cell lines, namely human hepatocellular carcinoma (HEPG2), human prostate cancer (PC3), and none-small cell lung cancer (A549) cell lines. An in vivo study using diethylnitrosamine (DENA)-induced HCC in adult male Wistar rats was conducted to investigate the potential antitumor activity of ZnONPs in HCC and the possible underlying mechanisms. Hepatocellular carcinoma (HCC) was induced by oral administration of DENA given in drinking water (100 mg/L) for 8 weeks. Rats were allocated into four groups, namely a control group, an HCC control group receiving DENA alone, a ZnONPs (10 μg/kg per week, intravenous (i.v.) for 1 month) control group, and a ZnONPs treatment group (receiving ZnONPs + DENA). ZnONPs significantly reduced the elevated serum levels of HCC-related tumor markers alphafetoprotein and alpha-l-fucosidase and the apoptotic marker caspase-3 compared with the untreated HCC rats. In addition, treatment with ZnONPs significantly decreased the elevated levels of hepatocyte integrity and oxidative stress markers as compared with the untreated HCC control group. Furthermore, the histopathological study revealed anaplasia and fibrous degenerations which were significantly corrected by ZnONPs treatment. In conclusion, administration of ZnONPs exhibited a promising preclinical anticancer efficacy in HCC and could be considered as a novel strategy for the treatment HCC in clinical practices.

A novel chemoprotective effect of tiopronin against diethylnitrosamine‐induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK‐P53 signalling cascade

“…This was evidenced by a significant decrease in CAT and GPx activities, as well as increase of NO and MDA levels in animals treated with DENA. These findings are in agreement with previous studies reporting that DENA‐induced oxidative stress plays a significant role in hepatocarcinogenesis …”

“…These findings are in agreement with previous studies reporting that DENA-induced oxidative stress plays a significant role in hepatocarcinogenesis. 29,[40][41][42] Interestingly, the current study found that tiopronin protected against DENA-induced HCC. We observed an improvement in the liver functions, a significant decrease in the relative liver weight and serum AFP level in addition to the alleviation of the macro-and microscopic features of HCC after tiopronin administration.…”

“…In our study, HCC was induced chemically in rats by the well‐established DENA model . In this model, administration of DENA to Wistar rats in the drinking water for 8 weeks was reported as a complete hepatocarcinogen for HCC induction in which DENA can function as both tumour initiator and promoter simultaneously .…”

“…In our study, HCC was induced chemically in rats by the well-established DENA model. 28,29 In this model, administration of DENA to Wistar rats in the drinking water for 8 weeks was reported as a complete hepatocarcinogen for HCC induction in which DENA can function as both tumour initiator and promoter simultaneously. 13,30 We employed this particular model due to its ease of applicability over the other routes of administration such as oral gavage 31 or intraperitoneal injection of DENA 32,33 in which the latter may additionally produce a drug-drug interaction with the intraperitoneally injected tiopronin or combining DENA with other drugs as sodium phenobarbital or thioacetamide.…”

Surface functionalization-specific binding of coagulation factors by zinc oxide nanoparticles delays coagulation time and reduces thrombin generation potential in vitro

“…ZnO NPs or ZnO-composites are applied for vaccine adjuvant use because the particulate form of NPs can efficiently deliver antigens to dendritic cells with subsequent adequate inflammatory responses [27, 28]. ZnO NPs have also been proposed as therapeutic agents in cancer [29–31] and inflammation [32]. However, the direct contact of ZnO NPs with blood components such as platelets can be critical in some instances, involving platelet activation and thrombus generation, but there is little information about the impact of size and surface functionalization of ZnO NPs on platelet homeostasis.…”