Zinc sulfide nanoparticles selectively induce cytotoxic and genotoxic effects on leukemic cells: involvement of reactive oxygen species and tumor necrosis factor alpha

Abstract

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.

Cobalt oxide nanoparticles induced oxidative stress linked to activation of TNF‐α/caspase‐8/p38‐MAPK signaling in human leukemia cells

“…For size measurement, sonicated stock solutions of all CoO NPs (0.5 mg ml –1 ) were diluted 20 times. Transmission electron microscopy was used to characterize the size and the shape of the CoO NPs (Dash et al ., ).…”

Toxicity of cobalt oxide nanoparticles to normal cells; an in vitro and in vivo study

“…cysteine (NAC; Sigma-Aldrich) was made with sterile water and 318 added to cells at 5 and 10 mM for 1 h[19]. After NAC pretreatment, 319 cells were cultured with CoO NPs for 24 h. Viability was deter-320 mined by the MTT method.Estimation of Co 2+ concentration in lymphocytes after treat-323 ment with CoO NPs was estimated by AAS.…”

“…The cells were resuspended in 6 M nitric 328 acid and incubated at 95°C C for 24 h. Acid digested samples were 329 then assayed for Co 2+ content with a Shimadzu AA-7000 atomic Á6H 2 O salt, dissolved in RPMI 1640 medium.The final cellular Co 2+ contents before and after treatment with CoO NPs were estimated from the standard curve. The Co 2+ con-335 tents of all buffers and culture medium were normalized to obtain 336 the actual Co 2+ content of the cells[17,19].…”

Self assembled nano fibers of betulinic acid: A selective inducer for ROS/TNF-alpha pathway mediated leukemic cell death

“…ROS measurement was performed using H 2 DCFDA according to our previously reported method [18]. In brief, normal PBL, KG-1A and K562 cell lines (2X 10 5 cells per milliliter) were treated with SA-BA at 25 µg/ml for 24 hrs.…”

“…After the treatment schedule cells were washed two times with culture medium and cell viability was estimated by MTT assay [16]. 18 Protein was determined according to Lowry et al, 1951 using bovine serum albumin as Standard [27].…”