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Cuprous oxide nanoparticles selectively induce apoptosis of tumor cells.

Wang Y, Zi XY, Su J, Zhang HX, Zhang XR, Zhu HY, Li JX, Yin M, Yang F, Hu YP - Int J Nanomedicine (2012)

Bottom Line: In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects.Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis.CONPs can also produce reactive oxygen species (ROS) and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Second Military Medical University, Shanghai, People's Republic of China.

ABSTRACT
In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects. Cuprous oxide nanoparticles (CONPs) can selectively induce apoptosis and suppress the proliferation of tumor cells, showing great potential as a clinical cancer therapy. Treatment with CONPs caused a G1/G0 cell cycle arrest in tumor cells. Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis. CONPs can also produce reactive oxygen species (ROS) and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells. Our results demonstrate that CONPs have selective cytotoxicity towards tumor cells, and indicate that CONPs might be a potential nanomedicine for cancer therapy.

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Differential cytotoxicity of CONPs on tumor cell (melanoma cells YUMAC), paired control tumor cell (HeLa), and normal cells (293T and MEF) detected by MTT assay.Notes: HeLa cells and melanoma cells were more sensitive, and the two normal cell lines (293T and MEF cells) were tolerant, especially at low concentrations. Cells were treated with the CONPs for 48 hours (*P < 0.005, n = 3).Abbreviations: CONPs, cuprous oxide nanoparticles; MEF, mouse embryonic fibroblast.
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f5-ijn-7-2641: Differential cytotoxicity of CONPs on tumor cell (melanoma cells YUMAC), paired control tumor cell (HeLa), and normal cells (293T and MEF) detected by MTT assay.Notes: HeLa cells and melanoma cells were more sensitive, and the two normal cell lines (293T and MEF cells) were tolerant, especially at low concentrations. Cells were treated with the CONPs for 48 hours (*P < 0.005, n = 3).Abbreviations: CONPs, cuprous oxide nanoparticles; MEF, mouse embryonic fibroblast.

Mentions: To solve this fundamental issue and to investigate the potential uses of CONPs as cancer therapeutics, an MTT assay was used to evaluate how CONPs affect the viability of HeLa cells and melanoma cells with normal human 293T cells and MEF cells as control. CONPs exhibited dose-dependent cytotoxicity in HeLa cells with a half-maximal inhibitory concentration (IC50) of 8.28 μg/mL, and in melanoma cells with IC50 of 1.533 μg/mL, whereas the IC50 values in MEF cells and 293T cells were 27.00 μg/mL and 14.22 μg/mL, respectively. The cancerous HeLa cells and melanoma cells displayed a strikingly greater sensitivity to the CONPs than the normal human (293T) or mouse (MEF) cell lines did (P < 0.005) (Figure 5). At low concentrations, lower than 5 μg/mL, there was a discriminative difference in the level of cytotoxicity between tumor cells and normal cells. Differential cytotoxicity is important because one of the greatest challenges facing chemotherapy is the inability of anticancer drugs to distinguish effectively between tumor cells and normal cells. In our study, low concentrations of CONPs selectively killed tumor cells, suggesting that CONPs may be useful as a potential anticancer drug. In addition to CONPs, ZnO nanoparticles also have selective toxicity against human myeloblastic leukemia cells (HL60) and show less toxicity against normal peripheral blood mononuclear cells.15 Therefore, CONPs may have a potential utility in the treatment of cancer, as do ZnO nanoparticles. Research has also shown that iron core-gold shell NPs have cancer cell-specific cytotoxicity.16 Referring to the periodic table of elements, it is not difficult to understand these results. Zn(II) and Cu(I) have a similar extranuclear electron assignment, which may contribute to their similar properties. Therefore, we can conjecture that the chemical and physical properties of these nanomedicines provide the basis of their biological action. Furthermore, some research has reported that the tumor cells were unable to clear the nanoparticles, but this result was different in the normal cells.30 In our experiment, the inability to clear CONPs might be one of the mechanisms that caused CONPs to show selective cytotoxicity against tumor cells.


Cuprous oxide nanoparticles selectively induce apoptosis of tumor cells.

Wang Y, Zi XY, Su J, Zhang HX, Zhang XR, Zhu HY, Li JX, Yin M, Yang F, Hu YP - Int J Nanomedicine (2012)

Differential cytotoxicity of CONPs on tumor cell (melanoma cells YUMAC), paired control tumor cell (HeLa), and normal cells (293T and MEF) detected by MTT assay.Notes: HeLa cells and melanoma cells were more sensitive, and the two normal cell lines (293T and MEF cells) were tolerant, especially at low concentrations. Cells were treated with the CONPs for 48 hours (*P < 0.005, n = 3).Abbreviations: CONPs, cuprous oxide nanoparticles; MEF, mouse embryonic fibroblast.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368515&req=5

f5-ijn-7-2641: Differential cytotoxicity of CONPs on tumor cell (melanoma cells YUMAC), paired control tumor cell (HeLa), and normal cells (293T and MEF) detected by MTT assay.Notes: HeLa cells and melanoma cells were more sensitive, and the two normal cell lines (293T and MEF cells) were tolerant, especially at low concentrations. Cells were treated with the CONPs for 48 hours (*P < 0.005, n = 3).Abbreviations: CONPs, cuprous oxide nanoparticles; MEF, mouse embryonic fibroblast.
Mentions: To solve this fundamental issue and to investigate the potential uses of CONPs as cancer therapeutics, an MTT assay was used to evaluate how CONPs affect the viability of HeLa cells and melanoma cells with normal human 293T cells and MEF cells as control. CONPs exhibited dose-dependent cytotoxicity in HeLa cells with a half-maximal inhibitory concentration (IC50) of 8.28 μg/mL, and in melanoma cells with IC50 of 1.533 μg/mL, whereas the IC50 values in MEF cells and 293T cells were 27.00 μg/mL and 14.22 μg/mL, respectively. The cancerous HeLa cells and melanoma cells displayed a strikingly greater sensitivity to the CONPs than the normal human (293T) or mouse (MEF) cell lines did (P < 0.005) (Figure 5). At low concentrations, lower than 5 μg/mL, there was a discriminative difference in the level of cytotoxicity between tumor cells and normal cells. Differential cytotoxicity is important because one of the greatest challenges facing chemotherapy is the inability of anticancer drugs to distinguish effectively between tumor cells and normal cells. In our study, low concentrations of CONPs selectively killed tumor cells, suggesting that CONPs may be useful as a potential anticancer drug. In addition to CONPs, ZnO nanoparticles also have selective toxicity against human myeloblastic leukemia cells (HL60) and show less toxicity against normal peripheral blood mononuclear cells.15 Therefore, CONPs may have a potential utility in the treatment of cancer, as do ZnO nanoparticles. Research has also shown that iron core-gold shell NPs have cancer cell-specific cytotoxicity.16 Referring to the periodic table of elements, it is not difficult to understand these results. Zn(II) and Cu(I) have a similar extranuclear electron assignment, which may contribute to their similar properties. Therefore, we can conjecture that the chemical and physical properties of these nanomedicines provide the basis of their biological action. Furthermore, some research has reported that the tumor cells were unable to clear the nanoparticles, but this result was different in the normal cells.30 In our experiment, the inability to clear CONPs might be one of the mechanisms that caused CONPs to show selective cytotoxicity against tumor cells.

Bottom Line: In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects.Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis.CONPs can also produce reactive oxygen species (ROS) and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Second Military Medical University, Shanghai, People's Republic of China.

ABSTRACT
In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects. Cuprous oxide nanoparticles (CONPs) can selectively induce apoptosis and suppress the proliferation of tumor cells, showing great potential as a clinical cancer therapy. Treatment with CONPs caused a G1/G0 cell cycle arrest in tumor cells. Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis. CONPs can also produce reactive oxygen species (ROS) and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells. Our results demonstrate that CONPs have selective cytotoxicity towards tumor cells, and indicate that CONPs might be a potential nanomedicine for cancer therapy.

Show MeSH
Related in: MedlinePlus