Limits...
Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells.

Chen F, Zhang XH, Hu XD, Zhang W, Lou ZC, Xie LH, Liu PD, Zhang HQ - Int J Nanomedicine (2015)

Bottom Line: NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death.However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials.These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.

View Article: PubMed Central - PubMed

Affiliation: College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, People's Republic of China.

ABSTRACT
Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF-7 breast cancer cells, and the efficacy and mechanisms of action of this combined treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death. However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials. These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.

No MeSH data available.


Related in: MedlinePlus

Enhancement of radiation-induced apoptosis by NGA, CNPs, and NGA-CNPs.Notes: (A) MCF-7 cells were exposed to indicated concentrations of NGA/CNPs/NGA-CNPs or 6 Gy radiation or both, and stained with annexin V–FITC/PI before flow cytometry analysis. In each plot, the lower left corner shows annexin V-/PI-negative cells (living cells); the lower right corner shows annexin V-positive cells (apoptotic cells); the top right corner shows PI-positive cells (dead cells with membranes permeable to PI) stained with annexin V; and the top left corner shows dissociated nuclei. (B) Quantitative analysis of dead vs living cells. Data were analyzed by analysis of ANOVA followed by the Bonferroni post hoc test. **P<0.01, and ***P<0.0001, the groups compared with vehicle control group; ##P<0.01 and ###P<0.001, the NGA-CNP group compared with NGA group; ^^^P<0.001, the NGA-CNP group compared with CNP group.Abbreviations: NGA, neogambogic acid; CNP, ceria nanoparticle; NGA-CNP, ceria nanoparticle modified with neogambogic acid; FITC, fluorescein isothiocyanate; PI, propidium iodide; ANOVA, analysis of variance.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4542556&req=5

f5-ijn-10-4957: Enhancement of radiation-induced apoptosis by NGA, CNPs, and NGA-CNPs.Notes: (A) MCF-7 cells were exposed to indicated concentrations of NGA/CNPs/NGA-CNPs or 6 Gy radiation or both, and stained with annexin V–FITC/PI before flow cytometry analysis. In each plot, the lower left corner shows annexin V-/PI-negative cells (living cells); the lower right corner shows annexin V-positive cells (apoptotic cells); the top right corner shows PI-positive cells (dead cells with membranes permeable to PI) stained with annexin V; and the top left corner shows dissociated nuclei. (B) Quantitative analysis of dead vs living cells. Data were analyzed by analysis of ANOVA followed by the Bonferroni post hoc test. **P<0.01, and ***P<0.0001, the groups compared with vehicle control group; ##P<0.01 and ###P<0.001, the NGA-CNP group compared with NGA group; ^^^P<0.001, the NGA-CNP group compared with CNP group.Abbreviations: NGA, neogambogic acid; CNP, ceria nanoparticle; NGA-CNP, ceria nanoparticle modified with neogambogic acid; FITC, fluorescein isothiocyanate; PI, propidium iodide; ANOVA, analysis of variance.

Mentions: To determine the rate of apoptosis and cell mortality following combined treatment with NGA/CNPs/NGA-CNPs and radiation, cells were analyzed by annexin V/PI staining and flow cytometry. Annexin V–FITC is used as a nonquantitative probe to detect cell surface expression of phosphatidylserine, an early marker for apoptosis.37 PI permeates cells with a damaged cell membrane and is therefore used to identify apoptotic or necrotic cells.37 Pretreatment of cells with NGA-CNPs and radiation inhibited proliferation to a greater degree than radiation alone or combined NGA and radiation treatment, while pretreatment with CNPs and radiation-induced cell death to an extent similar to radiation alone (Figure 5). Radiation delivered at a dose of 6 Gy or treatment with 0.5 μg/mL NGA, 10 μg/mL CNP, or 10 μg/mL NGA-CNP induced death in 17.40%, 11.14%, 7.63%, and 8.13% of cells, respectively. However, 10 μg/mL NGA-CNPs combined with 6 Gy radiation increased cell death to 29.26% (percent apoptosis: 11.49%) (P<0.001 vs 6 Gy radiation only), while NGA or CNPs combined with radiation increased cell death only to 21.04% (percent apoptosis: 5.02%) and 18.73% (percent apoptosis: 9.09%), respectively. When an NGA-CNP concentration of 20 μg/mL was used in conjunction with 6 Gy radiation, the rate of cell death was 34.65% (percent apoptosis: 8.24%) (P<0.001 vs 6 Gy radiation only), whereas treatment with 20 μg/mL NGA-CNP alone did not increase cell death. These results confirm that NGA-CNP potentiates the radiation-induced death of cancer cells to a greater extent than NGA or CNP alone and is far less toxic than NGA, and can therefore reduce damage to surrounding tissue in radiation therapy. In subsequent experiments, we investigated the mechanism underlying the sensitization of cells to the effects of radiation by NGA-CNP.


Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells.

Chen F, Zhang XH, Hu XD, Zhang W, Lou ZC, Xie LH, Liu PD, Zhang HQ - Int J Nanomedicine (2015)

Enhancement of radiation-induced apoptosis by NGA, CNPs, and NGA-CNPs.Notes: (A) MCF-7 cells were exposed to indicated concentrations of NGA/CNPs/NGA-CNPs or 6 Gy radiation or both, and stained with annexin V–FITC/PI before flow cytometry analysis. In each plot, the lower left corner shows annexin V-/PI-negative cells (living cells); the lower right corner shows annexin V-positive cells (apoptotic cells); the top right corner shows PI-positive cells (dead cells with membranes permeable to PI) stained with annexin V; and the top left corner shows dissociated nuclei. (B) Quantitative analysis of dead vs living cells. Data were analyzed by analysis of ANOVA followed by the Bonferroni post hoc test. **P<0.01, and ***P<0.0001, the groups compared with vehicle control group; ##P<0.01 and ###P<0.001, the NGA-CNP group compared with NGA group; ^^^P<0.001, the NGA-CNP group compared with CNP group.Abbreviations: NGA, neogambogic acid; CNP, ceria nanoparticle; NGA-CNP, ceria nanoparticle modified with neogambogic acid; FITC, fluorescein isothiocyanate; PI, propidium iodide; ANOVA, analysis of variance.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542556&req=5

f5-ijn-10-4957: Enhancement of radiation-induced apoptosis by NGA, CNPs, and NGA-CNPs.Notes: (A) MCF-7 cells were exposed to indicated concentrations of NGA/CNPs/NGA-CNPs or 6 Gy radiation or both, and stained with annexin V–FITC/PI before flow cytometry analysis. In each plot, the lower left corner shows annexin V-/PI-negative cells (living cells); the lower right corner shows annexin V-positive cells (apoptotic cells); the top right corner shows PI-positive cells (dead cells with membranes permeable to PI) stained with annexin V; and the top left corner shows dissociated nuclei. (B) Quantitative analysis of dead vs living cells. Data were analyzed by analysis of ANOVA followed by the Bonferroni post hoc test. **P<0.01, and ***P<0.0001, the groups compared with vehicle control group; ##P<0.01 and ###P<0.001, the NGA-CNP group compared with NGA group; ^^^P<0.001, the NGA-CNP group compared with CNP group.Abbreviations: NGA, neogambogic acid; CNP, ceria nanoparticle; NGA-CNP, ceria nanoparticle modified with neogambogic acid; FITC, fluorescein isothiocyanate; PI, propidium iodide; ANOVA, analysis of variance.
Mentions: To determine the rate of apoptosis and cell mortality following combined treatment with NGA/CNPs/NGA-CNPs and radiation, cells were analyzed by annexin V/PI staining and flow cytometry. Annexin V–FITC is used as a nonquantitative probe to detect cell surface expression of phosphatidylserine, an early marker for apoptosis.37 PI permeates cells with a damaged cell membrane and is therefore used to identify apoptotic or necrotic cells.37 Pretreatment of cells with NGA-CNPs and radiation inhibited proliferation to a greater degree than radiation alone or combined NGA and radiation treatment, while pretreatment with CNPs and radiation-induced cell death to an extent similar to radiation alone (Figure 5). Radiation delivered at a dose of 6 Gy or treatment with 0.5 μg/mL NGA, 10 μg/mL CNP, or 10 μg/mL NGA-CNP induced death in 17.40%, 11.14%, 7.63%, and 8.13% of cells, respectively. However, 10 μg/mL NGA-CNPs combined with 6 Gy radiation increased cell death to 29.26% (percent apoptosis: 11.49%) (P<0.001 vs 6 Gy radiation only), while NGA or CNPs combined with radiation increased cell death only to 21.04% (percent apoptosis: 5.02%) and 18.73% (percent apoptosis: 9.09%), respectively. When an NGA-CNP concentration of 20 μg/mL was used in conjunction with 6 Gy radiation, the rate of cell death was 34.65% (percent apoptosis: 8.24%) (P<0.001 vs 6 Gy radiation only), whereas treatment with 20 μg/mL NGA-CNP alone did not increase cell death. These results confirm that NGA-CNP potentiates the radiation-induced death of cancer cells to a greater extent than NGA or CNP alone and is far less toxic than NGA, and can therefore reduce damage to surrounding tissue in radiation therapy. In subsequent experiments, we investigated the mechanism underlying the sensitization of cells to the effects of radiation by NGA-CNP.

Bottom Line: NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death.However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials.These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.

View Article: PubMed Central - PubMed

Affiliation: College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, People's Republic of China.

ABSTRACT
Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF-7 breast cancer cells, and the efficacy and mechanisms of action of this combined treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death. However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials. These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.

No MeSH data available.


Related in: MedlinePlus