Zinc sulfide nanoparticles selectively induce cytotoxic and genotoxic effects on leukemic cells: involvement of reactive oxygen species and tumor necrosis factor alpha.
The aim of the present study was to develop zinc sulfide nanoparticles (ZnS NPs) and to study their cytotoxicity against the KG-1A (human acute myeloid leukemia) cell line. ZnS NPs were synthesized using the pyrolytic method and characterized by X-ray diffraction, dynamic light scattering, surface zeta potential, scanning electron microscopy and atomic force microscopy. Cell viability study and flow cytometric analysis confirmed the potent cytotoxic effects of ZnS NPs on cancer cells in a dose-dependent fashion. Successful uptakes of ZnS NPs by leukemic cells were confirmed by phase contrast fluorescence microscopy. pH-dependent dissolution of ZnS NPs was done using atomic absorption microscopy to understand the cell-specific internalization of Zn(+) . This internalization of NPs facilitated the generation of excess reactive oxygen species (ROS), followed by tumor necrosis factor alpha (TNF-α) secretion which caused severe DNA damage as observed in the comet assay and altered the mitochondrial membrane potential (MMP) in leukemic cells. Surprisingly ZnS NPs had no toxic effects on normal lymphocytes at doses up to 50 µg ml(-1) . Pre-treatment with ROS and TNF-α inhibitor confirmed that these nanoparticles were able to kill leukemic cells by generating an excess amount of ROS and thereby initiated TNF-α mediated apoptosis pathway. These findings clarify the mechanism with which ZnS NPs induced anticancer activities in vitro. To elicit its utilities and its application to cancer treatment in vivo is under investigation.
Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore-721 102, West Bengal, India.
Sandeep Kumar
SK
Dash
Totan
T
Ghosh
Soumyabrata
S
Roy
Sourav
S
Chattopadhyay
Debasis
D
Das
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D053758:Nanoparticles / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013440:Sulfides / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D017967:Zinc Compounds / Q000633:toxicity*
D017382:Reactive Oxygen Species; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; D017967:Zinc Compounds; D005978:Glutathione; C031238:zinc sulfide
TNF-α; cytotoxicity; genotoxic; mitochondrial membrane potential; pyrolytic; reactive oxygen species; redox balance; zinc sulfide nanoparticles