Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2)

Sharma, Vyom; Anderson, Diana; Dhawan, Alok

doi:10.1007/s10495-012-0705-6

Cited by 677 publications

(453 citation statements)

References 56 publications

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“…Thus, the results of the present study indicate that 23,24-dihydrocucurbitacin B may induce apoptosis by increasing intracellular ROS and decreasing the ΔΨm. Several anticancer drugs act against cancer by producing ROS (21,22); for example, afferent A disrupts the ΔΨm and induces oxidative stress, ultimately inducing apoptosis in osteosarcoma cells (23).…”

Section: Discussionmentioning

confidence: 99%

Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human cervical cell line is due to apoptosis and G2/M cell cycle arrest

Zhang

Hong

et al. 2018

Exp Ther Med

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Abstract. Cervical cancer is one of the primary causes of cancer-associated mortality worldwide. Due to the increasing incidence of cervical cancer, multiple treatment options are required. Initial responses to chemotherapy and surgical interventions are generally positive, however patients often experience relapse and tumor recurrence. Currently, the effects of cucurbitacins on different types of cancer are being investigated, as they exhibit a wide variety of bioactivities. The anticancer activity of the cucurbitacin 23,24-dihydrocucurbitacin B against a panel of human cervical cancer cell lines was investigated in the current study. Cell viability was determined using an MTT assay and apoptosis was detected using DAPI staining. The proportion of apoptotic cells, cell cycle distribution, mitochondrial membrane potential (ΔΨ m ) and reactive oxygen species (ROS) levels were estimated using flow cytometry. Protein expression was determined using western blot analysis. The results of the current study indicated that 23,24-dihydrocucurbitacin B inhibited the viability of human cervical cancer cell lines and had an IC 50 of 40-60 µM. However, its cytotoxic effects were much less pronounced in normal epithelial fr2 and HerEpiC cells, where it had an IC 50 of 125 µM. The underlying mechanisms of this were further studied and the results demonstrated that 23,24-dihydrocucurbitacin B induced apoptosis in HeLa cells and caused ROS-mediated shifts in the ΔΨ m . Additionally, it caused the cell cycle arrest of HeLa cells at the G 2 /M checkpoint. The phosphoinositide 3 kinase/protein kinase B/mechanistic target of rampamycin (PI3K/AKT/mTOR) cascade may serve an important role in cancer tumorigenesis, progression and resistance to chemotherapy. The results indicated that 23,24-dihydrocucurbitacin B significantly decreased the expression of important proteins in the PI3K/Akt/mTOR cascade. Taken together, these results suggest that 23,24-dihydrocucurbitacin B may be novel method of treating cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human cervical cell line is due to apoptosis and G2/M cell cycle arrest

Zhang

Hong

et al. 2018

Exp Ther Med

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“…Alterations in the Johnsen's scoring relate to germ cells degenerations. reported that ZNP exposure in HepG2 cells increases apoptotic cell death [36]. Recently, some NPs types have been identified as a novel class of autophagy activators and inducers of autophagic cell death [37,38].…”

Section: Discussionmentioning

confidence: 99%

The effect of zinc oxide nanoparticles on mouse spermatogenesis

Talebi

Khorsandi

Moridian³

2013

J Assist Reprod Genet

126

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Objective To evaluate the effects of zinc oxide nanoparticles on mouse spermatogenesis. Methods Thirty two adult male NMRI mice were used. Experimental Groups (ZNP-1-ZNP-3) received one of the following treatments daily for 35 days: 5, 50 and 300 mg/kg zinc oxide nanoparticles respectively. Control group received only distilled water. Epididymal sperm parameters, testicular histopathology, morphometric analysis and spermatogenesis assessments were performed for evaluation of the zinc oxide nanoparticles effects on testis. Results Epididymal sperm parameters including sperm number, motility and percentage of abnormality were significantly changed in 50 and 300 mg/kg zinc oxide nanoparticles treated mice (p<0.01). Histopathological criteria such as epithelial vacuolization, sloughing of germ and detachment were significantly increased in 50 and 300 mg/kg zinc oxide nanoparticles treated mice (p<0.001). 300 mg/kg zinc oxide nanoparticles induced formation of multinucleated giant cells in the germinal epithelium. 50 and 300 mg/kg zinc oxide nanoparticles also caused a significant decrease in seminiferous tubule diameter, seminiferous epithelium height and maturation arrest (p<0.001). Conclusion Zinc oxide nanoparticles act as testicular toxicant and further studies are needed to establish its mechanism of action upon spermatogenesis.

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“…This probe has been utilized successfully in previous investigations of ROS generation after exposure of different cells in vitro and ex vivo to a wide range of nano-sized materials (i.e. 9,32,35,37,46,[51][52][53]. Finally, it is important to further state that the flow cytometric evaluation of ROS is an established method and previously used in cell lines to detect NM-induced damage [54,55].…”

Section: Discussionmentioning

confidence: 99%

“…This property is believed to be size-dependent and only occurs at around 10-20 nm [7]. Iron oxide is one of the few NMs with current clinical applications and approved by the US Food and Drug Administration since 1996 [8,9].Carbon NM constructs and in particular carbon nanotubes are utilized in a diverse range of applications relevant to nanomedicine. These include implementation in drug or gene delivery systems [10][11][12][13], as targeting and photosensitizing agents [14], as tissue scaffolding [15], utilization in the treatment of arthritis [13] or to aid in imaging techniques [16][17][18].…”

mentioning

confidence: 99%

A Flow Cytometry‐based Method for the Screening of Nanomaterial‐induced Reactive Oxygen Species Production in Leukocytes Subpopulations in Whole Blood

Kermanizadeh

Jantzen

Brown

et al. 2017

Basic Clin Pharma Tox

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To date, the use and translation of nanomedicine from the laboratory to the clinic has been relatively slow. Among other issues, one of the reasons for this tardiness is the lack of the availability of quick and reliable toxicity tools for the screening of nanomaterials (NMs). In this investigation, we apply a flow cytometry-based method for the detection of nanomaterialinduced oxidative stress by measurement of reactive oxygen species production in specific leukocyte subpopulations in human whole blood. The screening of a panel of relevant nanomedical-associated materials (liposomes, silica, iron oxide and functionalized single-walled carbon nanotubes) demonstrated that only the carbon nanotubes induced oxidative stress in human circulating leukocytes. In summary, we apply and corroborate a flow cytometry-based method for the simple and effective measurement of NM-induced oxidative stress in human blood subpopulations after realistic and relevant exposure scenarios which is extremely useful in future toxicological applications.The rapid development of nanotechnology goes hand in hand with concerns about the potential adverse effects of nanomaterial (NM) exposure on human health and the environment. In addition, the apparent knowledge gaps in our understanding of the interaction between NMs and cells, their transformation and their eventual fate in different biological systems mean that hazard assessment is very challenging.Nanomedicine is defined as the application and utilization of nanotechnology to medicine and human health, in particular with regard to the diagnosis and treatment of disease. Over the last two decades, a wide range of NMs with varying size, shape, charge and other physicochemical characteristics are tailored to determine specific function, resulting in desirable optical, electronic, magnetic and biological attributes. The current nanomedicine applications mainly include vehicles for targeted drug delivery, NM platforms for biomedical imaging and therapeutic applications for treating clinical diseases [1,2]. Despite these promising medical applications, the safety concern for NMs is a key determinant factor in the assessment of their clinical potential. Therefore, it is imperative to implement risk reduction strategies for all materials proposed for medical applications. The same physicochemical characteristics that make NMs desirable for medical applications might contribute to their potential adverse effects -particle size and surface properties can largely influence the bioavailability, transport, biotransformation, cellular uptake and toxicity of the material in question [3,4].Iron oxide nanoparticles (NPs) can exhibit a unique form of superparamagnetism which is highly useful and desirable in biomedicine for several medical applications, principally relating to imaging and drug delivery to the central nervous system and various tumours [5,6]. This property is believed to be size-dependent and only occurs at around 10-20 nm [7]. Iron oxide is one of the few NMs with current clin...

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Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2)

Cited by 677 publications

References 56 publications

Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human cervical cell line is due to apoptosis and G2/M cell cycle arrest

Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human cervical cell line is due to apoptosis and G2/M cell cycle arrest

The effect of zinc oxide nanoparticles on mouse spermatogenesis

A Flow Cytometry‐based Method for the Screening of Nanomaterial‐induced Reactive Oxygen Species Production in Leukocytes Subpopulations in Whole Blood

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