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Apoptosis Induction By Silica Nanoparticles Mediated Through Reactive Oxygen Species In Human Liver Cell Line HepG2.

J. Ahmad, M. Ahamed, M. Akhtar, S. Alrokayan, M. A. Siddiqui, J. Musarrat, A. Al-Khedhairy
Published 2012 · Biology, Medicine

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Silica nanoparticles are increasingly utilized in various applications including agriculture and medicine. In vivo studies have shown that liver is one of the primary target organ of silica nanoparticles. However, possible mechanisms of hepatotoxicity caused by silica nanoparticles still remain unclear. In this study, we explored the reactive oxygen species (ROS) mediated apoptosis induced by well-characterized 14nm silica nanoparticles in human liver cell line HepG2. Silica nanoparticles (25-200μg/ml) induced a dose-dependent cytotoxicity in HepG2 cells. Silica nanoparticles were also found to induce oxidative stress in dose-dependent manner indicated by induction of ROS and lipid peroxidation and depletion of glutathione (GSH). Quantitative real-time PCR and immunoblotting results showed that both the mRNA and protein expressions of cell cycle checkpoint gene p53 and apoptotic genes (bax and caspase-3) were up-regulated while the anti-apoptotic gene bcl-2 was down-regulated in silica nanoparticles treated cells. Moreover, co-treatment of ROS scavenger vitamin C significantly attenuated the modulation of apoptotic markers along with the preservation of cell viability caused by silica nanoparticles. Our data demonstrated that silica nanoparticles induced apoptosis in human liver cells, which is ROS mediated and regulated through p53, bax/bcl-2 and caspase pathways. This study suggests that toxicity mechanisms of silica nanoparticles should be further investigated at in vivo level.
This paper references
10.1016/j.tiv.2010.01.001
Nano-SiO2 induces apoptosis via activation of p53 and Bax mediated by oxidative stress in human hepatic cell line.
Y. Ye (2010)
10.2217/17435889.3.1.5
Role of nanomedicines in cell-based therapeutics.
Z. Ye (2008)
10.1021/nn800596w
Cytotoxicity and genotoxicity of silver nanoparticles in human cells.
P. V. AshaRani (2009)
10.1016/j.tox.2011.04.010
Olaquindox induces apoptosis through the mitochondrial pathway in HepG2 cells.
Jiajie Zou (2011)
10.1016/0003-2697(79)90738-3
Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.
H. Ohkawa (1979)
10.1016/S0891-5849(99)00107-0
Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader.
Hongshun Wang (1999)
10.1007/S11051-009-9740-9
Toxicity of zinc oxide nanoparticles to zebrafish embryo: a physicochemical study of toxicity mechanism
W. Bai (2010)
10.1093/TOXSCI/KFG228
Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats.
D. Warheit (2004)
10.1016/j.cca.2010.08.016
Silver nanoparticle applications and human health.
M. Ahamed (2010)
10.1007/BF01666038
A simple quantitative procedure using monolayer cultures for cytotoxicity assays (HTD/NR-90)
E. Borenfreund (1985)
10.1016/j.colsurfb.2010.01.033
Signaling gene cascade in silver nanoparticle induced apoptosis.
P. Gopinath (2010)
10.1016/j.biomaterials.2010.10.035
Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in intravenously exposed mice.
Tianlong Liu (2011)
10.1093/TOXSCI/KFI216
The chemical species of aluminum influences its paracellular flux across and uptake into Caco-2 cells, a model of gastrointestinal absorption.
Yuzhao Zhou (2005)
10.1016/j.ejpb.2009.02.005
Silica nanoparticles as hepatotoxicants.
H. Nishimori (2009)
10.1093/toxsci/kfn072
Nominal and effective dosimetry of silica nanoparticles in cytotoxicity assays.
D. Lison (2008)
10.1016/j.tiv.2011.05.003
Size-dependent cytotoxicity of amorphous silica nanoparticles in human hepatoma HepG2 cells.
Y. Li (2011)
10.1369/jhc.2009.954446
Significance of Increased Apoptosis and Bax Expression in Human Small Intestinal Adenocarcinoma
C. Gao (2009)
10.1016/J.WATRES.2006.08.004
Comparative eco-toxicity of nanoscale TiO2, SiO2, and ZnO water suspensions.
L. K. Adams (2006)
10.1016/j.nano.2011.04.011
ZnO nanorod-induced apoptosis in human alveolar adenocarcinoma cells via p53, survivin and bax/bcl-2 pathways: role of oxidative stress.
M. Ahamed (2011)
10.1897/07-634.1
Ecotoxicity of silica nanoparticles to the green alga Pseudokirchneriella subcapitata: importance of surface area.
K. Van Hoecke (2008)
10.1016/j.addr.2008.03.012
Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers.
I. Slowing (2008)
10.1016/j.bbrc.2010.04.156
Genotoxic potential of copper oxide nanoparticles in human lung epithelial cells.
M. Ahamed (2010)
10.1289/ehp.10327
Meeting Report: Hazard Assessment for Nanoparticles—Report from an Interdisciplinary Workshop
J. Balbus (2007)
10.1016/j.taap.2008.09.015
DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells.
M. Ahamed (2008)
10.1038/nrm2308
The BCL-2 protein family: opposing activities that mediate cell death
R. Youle (2008)
10.1007/s00204-009-0488-x
Biodistribution and toxicity of intravenously administered silica nanoparticles in mice
Guangping Xie (2009)
10.1016/j.tiv.2010.03.002
The primary role of iron-mediated lipid peroxidation in the differential cytotoxicity caused by two varieties of talc nanoparticles on A549 cells and lipid peroxidation inhibitory effect exerted by ascorbic acid.
M. Akhtar (2010)
10.1088/0957-4484/22/5/055101
Integrated metabonomics analysis of the size-response relationship of silica nanoparticles-induced toxicity in mice.
X. Lu (2011)
10.1074/jbc.M413344200
Novel Role for Amphiregulin in Protection from Liver Injury*
C. Berasain (2005)
10.1016/j.toxlet.2010.07.009
In vitro evaluation of SiC nanoparticles impact on A549 pulmonary cells: cyto-, genotoxicity and oxidative stress.
S. Barillet (2010)
10.1016/j.tox.2011.03.001
Advances in metal-induced oxidative stress and human disease.
K. Jomová (2011)
10.1093/toxsci/kfn246
Subchronic inhalation toxicity of silver nanoparticles.
Jae Hyuck Sung (2009)
10.1016/0022-1759(83)90303-4
Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.
T. Mosmann (1983)
10.1093/TOXSCI/KFM240
Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique.
R. Murdock (2008)
10.1093/toxsci/kfp032
Safety evaluation of silver nanoparticles: inhalation model for chronic exposure.
S. Hussain (2009)
10.1016/j.tox.2011.02.010
Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells.
M. Ahamed (2011)
10.1016/0003-9861(59)90090-6
Tissue sulfhydryl groups.
G. Ellman (1959)
10.1007/S11051-008-9417-9
Toxicity of amorphous silica nanoparticles in mouse keratinocytes
K. Yu (2009)
10.1002/smll.200901403
Rattle-type Fe(3)O(4)@SiO(2) hollow mesoporous spheres as carriers for drug delivery.
Y. Zhu (2010)
10.1016/S0092-8674(03)01075-4
Principles of Tumor Suppression
C. Sherr (2004)
10.1038/nrc2522
Ageing, oxidative stress and cancer: paradigms in parallax
C. Benz (2008)
10.1016/j.taap.2009.10.016
Silver nanoparticles induced heat shock protein 70, oxidative stress and apoptosis in Drosophila melanogaster.
M. Ahamed (2010)
10.1016/j.jcis.2009.04.046
Cell toxicity of superparamagnetic iron oxide nanoparticles.
M. Mahmoudi (2009)
10.1016/j.tox.2010.07.010
Nanotoxicity of pure silica mediated through oxidant generation rather than glutathione depletion in human lung epithelial cells.
M. Akhtar (2010)
10.1016/j.tiv.2009.04.009
Oxidative stress contributes to silica nanoparticle-induced cytotoxicity in human embryonic kidney cells.
F. Wang (2009)
10.1016/j.aquatox.2009.11.016
Silver nanospheres are cytotoxic and genotoxic to fish cells.
J. P. Wise (2010)
10.1016/j.toxlet.2008.10.012
Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro.
E. Park (2009)
10.1126/SCIENCE.1114397
Toxic Potential of Materials at the Nanolevel
A. Nel (2006)
10.1093/TOXSCI/KFG243
Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation.
C. Lam (2004)
10.1016/j.nano.2009.03.003
In vitro proliferating cell models to study cytotoxicity of silica nanowires.
Daniel C. Julien (2010)
10.1016/j.biomaterials.2009.09.088
Size-mediated cytotoxicity and apoptosis of hydroxyapatite nanoparticles in human hepatoma HepG2 cells.
Y. Yuan (2010)
10.1074/JBC.273.16.9357
Caspase-3 Is Required for DNA Fragmentation and Morphological Changes Associated with Apoptosis*
R. Jänicke (1998)
10.1289/ehp.7339
Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles
G. Oberdörster (2005)
10.1021/jf8026827
Curcumin attenuates acrylamide-induced cytotoxicity and genotoxicity in HepG2 cells by ROS scavenging.
J. Cao (2008)
10.1016/j.tiv.2011.02.015
Toxic response of nickel nanoparticles in human lung epithelial A549 cells.
M. Ahamed (2011)
10.1016/j.lungcan.2010.06.002
Anticancer activity of Noscapine, an opioid alkaloid in combination with Cisplatin in human non-small cell lung cancer.
M. Chougule (2011)
10.1080/01926230601094552
Acute and Subacute Pulmonary Toxicity of Low Dose of Ultrafine Colloidal Silica Particles in Mice after Intratracheal Instillation
T. Kaewamatawong (2006)
10.1016/j.aquatox.2010.02.019
Assessment of uptake and toxicity of fluorescent silica nanoparticles in zebrafish (Danio rerio) early life stages.
K. Fent (2010)
10.2147/IJN.S
Quantum dot-doped silica nanoparticles as probes for targeting of T-lymphocytes
M. Bottini (2007)
10.1016/0003-2697(76)90527-3
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
M. M. Bradford (1976)
10.1016/j.canlet.2010.06.010
Ursolic acid induces doxorubicin-resistant HepG2 cell death via the release of apoptosis-inducing factor.
L. Yang (2010)



This paper is referenced by
10.1007/s00216-012-6246-6
The toxicity outcome of silica nanoparticles (Ludox®) is influenced by testing techniques and treatment modalities
C. Fede (2012)
10.1016/j.shaw.2013.07.006
Oxidative DNA Damage from Nanoparticle Exposure and Its Application to Workers' Health: A Literature Review
Kyung-Taek Rim (2013)
10.1080/15548627.2018.1509171
Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles
R. Mohammadinejad (2019)
10.2147/IJN.S224183
A reliable approach for assessing size-dependent effects of silica nanoparticles on cellular internalization behavior and cytotoxic mechanisms
Woo-Il Kim (2019)
10.3390/ijerph16173199
Co-Exposure to SiO2 Nanoparticles and Arsenic Induced Augmentation of Oxidative Stress and Mitochondria-Dependent Apoptosis in Human Cells
M. Ahamed (2019)
10.1038/srep13876
Aluminum doping tunes band gap energy level as well as oxidative stress-mediated cytotoxicity of ZnO nanoparticles in MCF-7 cells
M. Akhtar (2015)
10.1016/j.fct.2012.09.036
Herbacetin induces apoptosis in HepG2 cells: Involvements of ROS and PI3K/Akt pathway.
Y. Qiao (2013)
10.1021/acsomega.8b00608
Nanotoxicity of Silver Nanoparticles on HEK293T Cells: A Combined Study Using Biomechanical and Biological Techniques
Xuefeng Jiang (2018)
10.3390/nano9081172
Silica Nanoparticles Provoke Cell Death Independent of p53 and BAX in Human Colon Cancer Cells
Susanne Fritsch-Decker (2019)
10.1038/s41598-020-66644-z
Ultrafine silicon dioxide nanoparticles cause lung epithelial cells apoptosis via oxidative stress-activated PI3K/Akt-mediated mitochondria- and endoplasmic reticulum stress-dependent signaling pathways
kuan-I Lee (2020)
10.4110/in.2013.13.3.94
Immunostimulatory Effects of Silica Nanoparticles in Human Monocytes
Eun-Jeoung Yang (2013)
10.7314/APJCP.2014.15.12.4739
Nanoparticle induced oxidative stress in cancer cells: adding new pieces to an incomplete jigsaw puzzle.
D. Nogueira (2014)
10.1016/j.biomaterials.2012.06.016
Inflammasome formation and IL-1β release by human blood monocytes in response to silver nanoparticles.
Eun-Jeong Yang (2012)
Immunotoxicity of silicon dioxide nanoparticles with different size and electrostatic charge
Jae (2014)
10.1016/j.jhazmat.2014.01.028
Silica nanoparticles induce autophagy and autophagic cell death in HepG2 cells triggered by reactive oxygen species.
Y. Yu (2014)
10.2217/nnm.12.213
Attenuation of endothelial-dependent vasodilator responses, induced by dye-encapsulated silica nanoparticles, in aortic vessels.
A. Farooq (2014)
10.1002/PPSC.201400167
Cytotoxicity and Cellular Uptake of Amorphous Silica Nanoparticles in Human Cancer Cells
Y. Wu (2015)
10.1002/jbm.a.35333
Boron nitride nanotubes chemically functionalized with glycol chitosan for gene transfection in eukaryotic cell lines.
T. H. Ferreira (2015)
10.1016/j.taap.2013.09.001
Zinc ferrite nanoparticles activate IL-1b, NFKB1, CCL21 and NOS2 signaling to induce mitochondrial dependent intrinsic apoptotic pathway in WISH cells.
Q. Saquib (2013)
10.3892/mmr.2015.4603
Rhus javanica Linn protects against hydrogen peroxide‑induced toxicity in human Chang liver cells via attenuation of oxidative stress and apoptosis signaling.
Chanjin Yoon (2016)
10.3390/ijms20235846
Endoplasmic Reticulum Stress Cooperates in Silica Nanoparticles-Induced Macrophage Apoptosis via Activation of CHOP-Mediated Apoptotic Signaling Pathway
Fenglei Chen (2019)
10.12816/EJZ.2018.26954
THE TOXIC EFFECT OF MULTI WALL CARBON NANOTUBES ON SWISS ALBINO RAT
Safaa El-Sayed (2018)
Evaluation of the Role of Oxidative Stress, Inflammation and Apoptosis in the Pulmonary and the Hepatic Toxicity Induced by Cerium Oxide Nanoparticles Following Intratracheal Instillation in Male Sprague-Dawley Rats
Siva K. Nalabotu (2012)
In vitro toxicological assessment of amorphous silica particles in relation to their characteristics and mode of action in human skin cells
Claudia Moia (2015)
10.1016/j.chemosphere.2013.09.047
Nickel oxide nanoparticles exert cytotoxicity via oxidative stress and induce apoptotic response in human liver cells (HepG2).
M. Ahamed (2013)
10.4172/2167-0501.1000E122
Nanomadicine in Cancer Treatment: Drug Targeting and the Safety of the Used Materials for Drug Nanoencapsulation
D. Bikiaris (2012)
10.1016/j.chemosphere.2015.03.079
Comparative cytotoxic response of nickel ferrite nanoparticles in human liver HepG2 and breast MFC-7 cancer cells.
M. Ahamed (2015)
10.1039/C4EN00096J
Metabolomic effects in HepG2 cells exposed to four TiO2 and two CeO2 nanomaterials
K. Kitchin (2014)
10.2217/nnm-2017-0363
Doxorubicin and paclitaxel carried by methoxy poly(ethylene glycol)-poly(lactide-co-glycolide) is superior than traditional drug-delivery methods.
Yili Hu (2018)
10.1002/9781118856017.CH2
Considerations for In Vitro Nanotoxicity Testing
Athena M. Keene (2014)
10.1186/s12951-019-0456-4
Two distinct cellular pathways leading to endothelial cell cytotoxicity by silica nanoparticle size
Kyungmin Lee (2019)
10.2217/nnm-2018-0076
The toxicity of silica nanoparticles to the immune system.
L. Chen (2018)
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