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Copper oxide nanoparticles induced mitochondria mediated apoptosis in human hepatocarcinoma cells.

ABSTRACT: Copper oxide nanoparticles (CuO NPs) are heavily utilized in semiconductor devices, gas sensor, batteries, solar energy converter, microelectronics and heat transfer fluids. It has been reported that liver is one of the target organs for nanoparticles after they gain entry into the body through any of the possible routes. Recent studies have shown cytotoxic response of CuO NPs in liver cells. However, the underlying mechanism of apoptosis in liver cells due to CuO NPs exposure is largely lacking. We explored the possible mechanisms of apoptosis induced by CuO NPs in human hepatocellular carcinoma HepG2 cells. Prepared CuO NPs were spherical in shape with a smooth surface and had an average diameter of 22 nm. CuO NPs (concentration range 2-50 µg/ml) were found to induce cytotoxicity in HepG2 cells in dose-dependent manner, which was likely to be mediated through reactive oxygen species generation and oxidative stress. Tumor suppressor gene p53 and apoptotic gene caspase-3 were up-regulated due to CuO NPs exposure. Decrease in mitochondrial membrane potential with a concomitant increase in the gene expression of bax/bcl2 ratio suggested that mitochondria mediated pathway involved in CuO NPs induced apoptosis. This study has provided valuable insights into the possible mechanism of apoptosis caused by CuO NPs at in vitro level. Underlying mechanism(s) of apoptosis due to CuO NPs exposure should be further invested at in vivo level.

SUBMITTER: Siddiqui MA

PROVIDER: S-EPMC3734287 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Copper oxide nanoparticles induced mitochondria mediated apoptosis in human hepatocarcinoma cells.

Siddiqui Maqsood A MA Alhadlaq Hisham A HA Ahmad Javed J Al-Khedhairy Abdulaziz A AA Musarrat Javed J Ahamed Maqusood M

PloS one 20130805 8

Copper oxide nanoparticles (CuO NPs) are heavily utilized in semiconductor devices, gas sensor, batteries, solar energy converter, microelectronics and heat transfer fluids. It has been reported that liver is one of the target organs for nanoparticles after they gain entry into the body through any of the possible routes. Recent studies have shown cytotoxic response of CuO NPs in liver cells. However, the underlying mechanism of apoptosis in liver cells due to CuO NPs exposure is largely lacking ...[more]

PMID: 23940521

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Project description:PurposeThis study aims to prepare folic acid coated tin oxide nanoparticles (FA-SnO2 NPs) for specifically targeting human ovarian cancer cells with minimum side effects against normal cells.MethodsThe prepared FA-SnO2 NPs were characterized by FT-IR, UV-vis spectroscopy, XRD, SEM and TEM. The inhibition effects of FA-SnO2 NPs against SKOV3 cancer cell were tested by MTT and LDH assay. Apoptosis induction in FA-SnO2 NPs treated SKOV3 cells were investigated using Annexin V/PI, AO/EB and Comet assays and the possible mechanisms of the cytotoxic action were studied by Flow cytometry, qRT-PCR, Immunohistochemistry, and Western blotting analyses. The effects of FA-SnO2 NPs on reactive oxygen species generation in SKOV3 cells were also examined. Additionally, the safety of utilization FA-SnO2 NPs were studied in vivo using Wister rats.ResultsThe obtained FA-SnO2 NPs displayed amorphous spherical morphology with an average diameter of 157 nm and a zeta potential value of -24 mV. Comparing to uncoated SnO2 NPs, FA-SnO2 NPs had a superior inhibition effect towards SKOV3 cell growth that was suggested to be mediated through higher reactive oxygen species generation. It was showed that FA-SnO2 NPs increased significantly the % of apoptotic cells in the sub- G1 and G2/M phases with a higher intensity comet nucleus in SKOV3 treated cells. Furthermore, FA-SnO2 NPs was significantly increased the expression levels of P53, Bax, and cleaved Caspase-3 and accompanied with a significant decrease of Bcl-2 in the treated SKOV3 cells.ConclusionOverall, the results suggested that an increase in cellular FA-SnO2 NPs internalization resulted in a significant induced cytotoxicity in SKOV3 cancer cells in dose-dependent mode through ROS-mediated cell apoptosis that may have occurred through mitochondrial pathway. Additionally, the results confirmed the safety of utilization FA-SnO2 NPs against living systems. So, FA-SnO2 NPs with a specific targeting moiety may be a promising therapeutic candidate for human ovarian cancer.

Project description:The greatest challenge of the current generation and generations to come is antimicrobial resistance, as different pathogenic bacteria have continuously evolved to become resistant to even the most recently synthesized antibiotics such as carbapenems. Resistance to carbapenems limits the therapeutic options of MDR infections as they are the only safe and effective drugs recommended to treat such infections. This scenario has complicated treatment outcomes, even to the commonest bacterial infections. Repeated attempts to develop other approaches have been made. The most promising novel therapeutic option is the use of nanomaterials as antimicrobial agents. Thus, this study examined the efficacy of Camellia sinensis extract (CSE) and Prunus africana bark extract (PAE) green synthesized Copper oxide nanoparticles (CuONPs) against carbapenem-resistant bacteria. Furthermore, the photocatalytic and antioxidant activities of CuONPs were evaluated to determine the potential of using them in a wide range of applications. CuONPs were biosynthesized by CSE and PAE. UV vis spectroscopy, X-ray Diffraction (XRD), Dynamic light scattering (DLS), Fourier Transform Infrared spectroscopy (FTIR), and Scanning Electron Microscopy (SEM) were used to characterize the nanoparticles. CuONPs susceptibility tests were carried out by the agar well diffusion method. The photocatalytic and antioxidant activities of the CuONPs were determined by the methylene blue and DPPH free radical scavenging assays, respectively. UV vis absorbance spectra registered surface plasmon resonance peaks between 272 and 286 nm, confirming the presence of CuONPs. The XRD array had nine strong peaks at 2θ values typical of CuONPs. FTIR spectra exhibited bands associated with organic functional groups confirming capping and functionalization of the CuONPs by the phytochemicals. DLS analysis registered a net zeta potential of +12.5 mV. SEM analysis revealed that the nanoparticles were spherical and clustered with a mean diameter of 6 nm. Phytosynthesized CuONPs exhibited the highest growth suppression zones of 30 mm with MIC ranging from 30 to 125 μg/ml against MDR bacteria. Furthermore, the CuONPs achieved a methylene blue dye photocatalysis degradation efficiency of 85.5% and a free radical scavenging activity of 28.8%. PAE and CSE successfully bio-reduced copper ions to the nanoscale level with potent antimicrobial, photocatalysis, and antioxidant activities.

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Copper oxide nanoparticles induced mitochondria mediated apoptosis in human hepatocarcinoma cells.

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Copper oxide nanoparticles induced mitochondria mediated apoptosis in human hepatocarcinoma cells.

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