Silver-Based Nanoparticles Induce Apoptosis in Human Colon Cancer Cells Mediated Through P53

Satapathy, Shakti Ranjan; Mohapatra, Purusottam; Preet, Ranjan; Das, Diptikanta; Sarkar, Biplab; Choudhuri, Tathagata; Wyatt, Michael D.; Kundu, Chanakya Nath

doi:10.2217/nnm.12.176

Cited by 134 publications

(103 citation statements)

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“…It is also established that the induction of apoptosis by different cellular stresses is mediated via the MAPK cascades of JNK, Erk1/2, and p38 MAPK as well as the p53 pathway. [84][85][86] Therefore, we evaluated the effect of AgNPs on apoptosis and expression of apoptosis-related genes in TM3 and TM4 cells. Apoptosis was measured by flow cytometry in AgNPsexposed cells stained with propidium iodide and Annexin V. TM3 and TM4 cells treated with AgNPs showed an increase in cellular apoptosis ( Figure 9A and B), which was alleviated by the pretreatment with NAC.…”

Section: Effect Of Agnps On Signaling Molecules Involved In Apoptosismentioning

confidence: 99%

Differential nanoreprotoxicity of silver nanoparticles in male somatic cells and spermatogonial stem cells

Zhang¹,

Choi²,

Han³

et al. 2015

IJN

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Background Silver nanoparticles (AgNPs) possess unique physical, chemical, and biological properties. AgNPs have been increasingly used as anticancer, antiangiogenic, and antibacterial agents for the treatment of bacterial infections in open wounds as well as in ointments, bandages, and wound dressings. The present study aimed to investigate the effects of two different sizes of AgNPs (10 nm and 20 nm) in male somatic Leydig (TM3) and Sertoli (TM4) cells and spermatogonial stem cells (SSCs). Methods Here, we demonstrate a green and simple method for the synthesis of AgNPs using Bacillus cereus culture supernatants. The synthesized AgNPs were characterized using ultraviolet and visible absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy (TEM). The toxicity of the synthesized AgNPs was evaluated by the effects on cell viability, metabolic activity, oxidative stress, apoptosis, and expression of genes encoding steroidogenic and tight junction proteins. Results AgNPs inhibited the viability and proliferation of TM3 and TM4 cells in a dose- and size-dependent manner by damaging cell membranes and inducing the generation of reactive oxygen species, which in turn affected SSC growth on TM3 and TM4 as feeder cells. Small AgNPs (10 nm) were more cytotoxic than medium-sized nanoparticles (20 nm). TEM revealed the presence of AgNPs in the cell cytoplasm and nucleus, and detected mitochondrial damage and enhanced formation of autosomes and autolysosomes in the AgNP-treated cells. Flow cytometry analysis using Annexin V/propidium iodide staining showed massive cell death by apoptosis or necrosis. Real-time polymerase chain reaction and western blot analyses indicated that in TM3 and TM4 cells, AgNPs activated the p53, p38, and pErk1/2 signaling pathways and significantly downregulated the expression of genes related to testosterone synthesis (TM3) and tight junctions (TM4). Furthermore, the exposure of TM3 and TM4 cells to AgNPs inhibited proliferation and self-renewal of SSCs. Conclusion Our results suggest that AgNPs exhibit size-dependent nanoreprotoxicity in male somatic cells and SSCs, strongly suggesting that applications of AgNPs in commercial products must be carefully evaluated. Further studies of AgNPs-induced nanoreprotoxicity in animal models are required.

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Section: Effect Of Agnps On Signaling Molecules Involved In Apoptosismentioning

confidence: 99%

Differential nanoreprotoxicity of silver nanoparticles in male somatic cells and spermatogonial stem cells

Zhang¹,

Choi²,

Han³

et al. 2015

IJN

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“…The p53 pathway mediates TiO 2 NPs-induced apoptosis (Kang et al, 2008;Shi et al, 2010;Wu et al, 2010). There are a few reports that Ag-NPs induce apoptosis through p53 (Satapathy et al, 2013;Gopinath et al, 2010). Ag-NPs modulate apoptosis-related proteins and caused p53-dependent apoptosis in human colon carcinoma (HT29 and HCT116) cell -and HCT116 cells, respectively.…”

Section: It Is Critical To Assess Potential Impacts Of Nps Onmentioning

confidence: 99%

“…For example, Ag-NPs interact with the HIV-1 virus and inhibit its ability to bind host cells in vitro (Elechiguerra et al, 2005). Furthermore, Ag-NPs trigger in vitro apoptosis in human colon cancer cells (Satapathy et al, 2013;Gopinath et al, 2010). Therefore, understanding the potential toxicological impacts of AgNPs is important for development of the Ag-NP industry.…”

Section: Introductionmentioning

confidence: 99%

Silver nanoparticles induce p53-mediated apoptosis in human bronchial epithelial (BEAS-2B) cells

et al. 2014

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-Deregulated apoptosis has been associated with many lung diseases. Although many studies have reported the apoptotic effects exhibited by silver nanoparticles (Ag-NPs) in various circumstances, the apoptosis mechanism of Ag-NPs is unclear. We investigated oxidative stress and apoptosis in human normal bronchial epithelial (BEAS-2B) cells to elucidate the role of p53 in apoptosis by Ag-NPs. First, dispersion and stability of Ag-NPs improved using bronchial epithelial cell growth medium with 5% fetal bovine serum. Then, we observed oxidative stress in BEAS-2B cells exposed to Ag-NPs. Second, we carried out a cell death assay to measure DNA fragmentation as a biomarker of apoptosis. BEAS--mentation. We also found that apoptosis-related genes (caspase-3, Bax, and Bcl-2) were regulated by AgNPs, which was detected by mRNA and protein levels. These results suggest that Ag-NPs induced p53-Ag-NPs in pulmonary disease. Original ArticleThe Journal of Toxicological Sciences (J. Toxicol. Sci.) Vol.39, No.3, 401-412, 2014 Vol. 39 No. 3 401 lar and DNA damage (Risom et al., 2005). DNA damage induces extracellular and intracellular signals that trigger the onset of a signaling cascade with characteristic biochemical and morphological features, including nuclear condensation, membrane blebbing, and DNA fragmentation, leading ultimately to cell death (Johnson et al., 1996). This is called apoptosis, which is essential for the normal functioning and survival of multi-cellular organisms. However, deregulated apoptosis has been associated with many lung diseases because toxic contents are released from apoptotic cells unless the cells are quickly recognized or ingested by phagocytes (Pandya et al., 2006).The p53 gene regulates the apoptosis pathway (Korsmeyer, 1995;Yang and Duerksen-Hughes, 1998) and is tightly controlled through a complex series of events including translational regulation, interaction with regu--cations including multisite phosphorylation and acetylation (Giaccia and Kastan, 1998;Meek, 1999;Prives and Hall, 1999). In particular, phosphorylation of the serine-15 (Ser-15) residue due to DNA damage plays an important role in p53-mediated apoptosis (Dumaz and Meek, 1999;Siliciano et al., 1997;Unger et al., 1999). This activation of p53 leads to expression of its downstream effectors such as Bax, Bcl-2 and caspase-3, resulting in apoptosis (Martin and Elkon, 2004).In this study, we hypothesized that Ag-NPs induce apoptosis via the p53 signaling pathway in normal human lung bronchial epithelial (BEAS-2B) cells. Although many reports have shown apoptotic effects of Ag-NPs in various circumstances (Foldbjerg et al., 2009;Li et al., 2010;Miura and Shinohara, 2009;Piao et al., 2011), the were used to elucidate the role of p53 in apoptosis by Ag--sion of TiO 2 NPs improved by adding bovine serum albumin (BSA) or fetal bovine serum (FBS) to the medium (Ji et al., 2010). Thus, Ag-NPs were dispersed in bronchial epithelial growth medium (BEGM) with 5% FBS and were characterized. Then, we observed ROS generation...

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“…46 AgNPs increased ROS production in cells, leading to apoptosis through the activation of p42/p44, JNKs, or p38 mitogen-activated protein kinases or p53-dependent processes. 47,48 Because of the extensive use of AgNPs in consumer products and increasing potential of human and environmental exposure, safety and regulatory concerns regarding AgNPs are growing. 49,50 The primary objective of this study was to synthesize smaller AgNPs using biological systems.…”

Section: Introductionmentioning

confidence: 99%

Silver nanoparticles cause complications in pregnant mice

Zhang¹,

Park²,

Choi³

et al. 2015

IJN

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Background Silver nanoparticles (AgNPs) have attracted much interest and have been used for antibacterial, antifungal, anticancer, and antiangiogenic applications because of their unique properties. The increased usage of AgNPs leads to a potential hazard to human health. However, the potential effects of AgNPs on animal models are not clear. This study was designed to investigate the potential impact of AgNPs on pregnant mice. Methods The synthesis of AgNPs was performed using culture extracts of Bacillus cereus . The synthesized AgNPs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy. AgNPs were administrated into pregnant mice via intravenous infusion at 1.0 mg/kg doses at 6.5 days postcoitum (dpc). At 13.5, 15.5, and 17.5 dpc, the pregnant mice were euthanized, and the embryo and placenta were isolated. The meiotic status of oocytes was evaluated. DNA methylation studies were performed, and aberrant imprinting disrupted fetal, placental, and postnatal development. Quantitative real-time polymerase chain reaction analysis and Western blot were used to analyze various gene expressions. Results The synthesized AgNPs were uniformly distributed and were spherical in shape with an average size of 8 nm. AgNPs exposure increased the meiotic progression of female germ cells in the fetal mouse ovaries, and maternal AgNP exposure significantly disrupted imprinted gene expression in 15.5 dpc embryos and placentas, such as Ascl2 , Snrpn , Kcnq1ot1 , Peg3 , Zac1 , H19 , Igf2r , and Igf2 ; DNA methylation studies revealed that AgNPs exposure significantly altered the methylation levels of differentially methylated regions of Zac1 . Conclusion The results from this study indicated that early exposure to AgNPs has the potential to disrupt fetal and postnatal health through epigenetic changes in the embryo and abnormal development of the placenta. These results can contribute to research involved in the safe use of various biomedical applications of AgNPs and improves the understanding of the development of AgNPs in biomedical applications.

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Silver-Based Nanoparticles Induce Apoptosis in Human Colon Cancer Cells Mediated Through P53

Abstract: AgNPs are bona fide anticancer agents that act in a p53-dependent manner. Original submitted 16 March 2012; Revised submitted 25 August 2012; Published online 21 March 2013.

Cited by 134 publications

References 39 publications

Differential nanoreprotoxicity of silver nanoparticles in male somatic cells and spermatogonial stem cells

Differential nanoreprotoxicity of silver nanoparticles in male somatic cells and spermatogonial stem cells

Silver nanoparticles induce p53-mediated apoptosis in human bronchial epithelial (BEAS-2B) cells

Silver nanoparticles cause complications in pregnant mice

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