Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species

Abstract

Background: Zinc oxide nanoparticles (ZnO NPs) have received much attention for their implications in cancer therapy. It has been reported that ZnO NPs induce selective killing of cancer cells. However, the underlying molecular mechanisms behind the anticancer response of ZnO NPs remain unclear. Methods and results:We investigated the cytotoxicity of ZnO NPs against three types of cancer cells (human hepatocellular carcinoma HepG2, human lung adenocarcinoma A549, and human bronchial epithelial BEAS-2B) and two primary rat cells (astrocytes and hepatocytes). Results showed that ZnO NPs exert distinct effects on mammalian cell viability via killing of all three types of cancer cells while posing no impact on normal rat astrocytes and hepatocytes. The toxicity mechanisms of ZnO NPs were further investigated using human liver cancer HepG2 cells. Both the mRNA and protein levels of tumor suppressor gene p53 and apoptotic gene bax were upregulated while the antiapoptotic gene bcl-2 was downregulated in ZnO NPtreated HepG2 cells. ZnO NPs were also found to induce activity of caspase-3 enzyme, DNA fragmentation, reactive oxygen species generation, and oxidative stress in HepG2 cells. Conclusion:Overall, our data demonstrated that ZnO NPs selectively induce apoptosis in cancer cells, which is likely to be mediated by reactive oxygen species via p53 pathway, through which most of the anticancer drugs trigger apoptosis. This study provides preliminary guidance for the development of liver cancer therapy using ZnO NPs.

Investigation on cellular interactions of astrocytes with zinc oxide nanoparticles using rat C6 cell lines

“…In this study MTT assay and neutral red uptake assay was used to were evaluated. This study shows a significant reduction in cell viability for HepG2, A549 and BEAS-2B cells at 10 μg/ml and 15 μg/ml of ZnO NPs after 24h treatment [52]. The present results also show similar dosimetry.…”

Significance of polymethylmethacrylate (PMMA) modification by zinc oxide nanoparticles for fungal biofilm formation

“…Studies show that on the one hand, ZnO increases the intracellular concentration of reactive oxygen species (ROS) while on the other Zn 2+ ions induce the overproduction of apoptotic tumor suppressor protein p53 (Meyer et al, 2011). Interestingly, ZnO nanoparticles induce death of human cancer cells in the ROS mechanism without damaging normal cells (Akhtar et al, 2012). The effect of ZnO on the fungal biofilm formation was investigated using a classical method, namely staining with crystal violet.…”

Phytoextract-mediated synthesis of zinc oxide nanoparticles using aqueous leaves extract of Ipomoea pes-caprae (L).R.br revealing its biological properties and photocatalytic activity

“…The zinc ions might explain ZnO-induced cytotoxic and apoptotic activity. Zinc ions released from ZnO materials induce oxidative stressmediated cell death [7][8][9], and the strong correlation between ZnO NPs-induced cytotoxicity and free zinc ion concentration also suggests a requirement for ZnO dissolution for effective cytotoxicity [10]. A number of studies have reported the toxicity of ZnO materials, and their potential to induce cell death has been explored in cancer biology [7,11].…”