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 NP-treated 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.

• Authors: Mohd Javed Akhtar, Maqusood Ahamed, Sudhir Kumar, Ma Majeed Khan, Javed Ahmad, Salman A Alrokayan
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 7 Pg. 845-57 ( 2012) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 22393286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Antioxidants
• Apoptosis Regulatory Proteins
• RNA, Messenger
• Reactive Oxygen Species
• TP53 protein, human
• Tumor Suppressor Protein p53
• Zinc Oxide

Topics

• Analysis of Variance
• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Antioxidants (metabolism)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Cell Line, Tumor
• Cell Survival
• Cells, Cultured
• DNA Fragmentation
• Hep G2 Cells
• Humans
• Metal Nanoparticles (chemistry)
• RNA, Messenger (metabolism)
• Rats
• Reactive Oxygen Species (metabolism)
• Spectrophotometry, Ultraviolet
• Tumor Suppressor Protein p53 (metabolism)
• Zinc Oxide (chemistry, pharmacology)