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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

Autophagy in MCF-7 cells treated with NGA-CNPs and radiation.Notes: (A) Cells were incubated with indicated concentrations of NGA-CNPs for 24 hours followed by exposure to indicated doses of radiation; 24 hours later, cells were stained Cyto-ID (green) for detection of autophagic vacuoles and counterstained with Hoechst 33342 to label nuclei. (B) Quantitative analysis of autophagic cells (ie, with at least three green dots or a green cluster). Data were analyzed by analysis of ANOVA followed by Bonferroni post hoc test. ***P<0.0001, the groups compared with vehicle control groups (0 μg/mL +0 Gy group, or 0 μg/mL +6 Gy group).Abbreviations: NGA-CNP, ceria nanoparticle modified with neogambogic acid; ANOVA, analysis of variance.
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f7-ijn-10-4957: Autophagy in MCF-7 cells treated with NGA-CNPs and radiation.Notes: (A) Cells were incubated with indicated concentrations of NGA-CNPs for 24 hours followed by exposure to indicated doses of radiation; 24 hours later, cells were stained Cyto-ID (green) for detection of autophagic vacuoles and counterstained with Hoechst 33342 to label nuclei. (B) Quantitative analysis of autophagic cells (ie, with at least three green dots or a green cluster). Data were analyzed by analysis of ANOVA followed by Bonferroni post hoc test. ***P<0.0001, the groups compared with vehicle control groups (0 μg/mL +0 Gy group, or 0 μg/mL +6 Gy group).Abbreviations: NGA-CNP, ceria nanoparticle modified with neogambogic acid; ANOVA, analysis of variance.

Mentions: Cells were incubated with NGA-CNPs for 24 hours, exposed to 6 Gy radiation, and then labeled with Cyto-ID as well as Hoechst 33342 to detect nuclei. Quantitative analysis of autophagic cells is shown in Figure 7. Cells containing at least three green dots or a green cluster corresponding to microtubule-associated light chain protein 3 (LC3) puncta were determined as autophagic cells; at least 150 cells were counted in triplicate samples.15 Exposure to radiation or 10 μg/mL or 20 μg/mL NGA-CNPs alone did not lead to the obvious formation of LC3-positive puncta in confocal images (Figure 7). However, a combination of NGA-CNP and 6 Gy radiation increased the number of LC3-positive puncta relative to those treated with radiation alone (P<0.001 vs 6 Gy radiation only). These results were confirmed by flow cytometry and suggest that the enhancement of autophagy is a mechanism by which NGA-CNPs sensitize cancer cells to the effects of radiation (Figure 8). However, additional studies are needed to determine the relationship between the induction of autophagy and the increased rate of cell death.


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)

Autophagy in MCF-7 cells treated with NGA-CNPs and radiation.Notes: (A) Cells were incubated with indicated concentrations of NGA-CNPs for 24 hours followed by exposure to indicated doses of radiation; 24 hours later, cells were stained Cyto-ID (green) for detection of autophagic vacuoles and counterstained with Hoechst 33342 to label nuclei. (B) Quantitative analysis of autophagic cells (ie, with at least three green dots or a green cluster). Data were analyzed by analysis of ANOVA followed by Bonferroni post hoc test. ***P<0.0001, the groups compared with vehicle control groups (0 μg/mL +0 Gy group, or 0 μg/mL +6 Gy group).Abbreviations: NGA-CNP, ceria nanoparticle modified with neogambogic acid; ANOVA, analysis of variance.
© Copyright Policy
Related In: Results  -  Collection

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

f7-ijn-10-4957: Autophagy in MCF-7 cells treated with NGA-CNPs and radiation.Notes: (A) Cells were incubated with indicated concentrations of NGA-CNPs for 24 hours followed by exposure to indicated doses of radiation; 24 hours later, cells were stained Cyto-ID (green) for detection of autophagic vacuoles and counterstained with Hoechst 33342 to label nuclei. (B) Quantitative analysis of autophagic cells (ie, with at least three green dots or a green cluster). Data were analyzed by analysis of ANOVA followed by Bonferroni post hoc test. ***P<0.0001, the groups compared with vehicle control groups (0 μg/mL +0 Gy group, or 0 μg/mL +6 Gy group).Abbreviations: NGA-CNP, ceria nanoparticle modified with neogambogic acid; ANOVA, analysis of variance.
Mentions: Cells were incubated with NGA-CNPs for 24 hours, exposed to 6 Gy radiation, and then labeled with Cyto-ID as well as Hoechst 33342 to detect nuclei. Quantitative analysis of autophagic cells is shown in Figure 7. Cells containing at least three green dots or a green cluster corresponding to microtubule-associated light chain protein 3 (LC3) puncta were determined as autophagic cells; at least 150 cells were counted in triplicate samples.15 Exposure to radiation or 10 μg/mL or 20 μg/mL NGA-CNPs alone did not lead to the obvious formation of LC3-positive puncta in confocal images (Figure 7). However, a combination of NGA-CNP and 6 Gy radiation increased the number of LC3-positive puncta relative to those treated with radiation alone (P<0.001 vs 6 Gy radiation only). These results were confirmed by flow cytometry and suggest that the enhancement of autophagy is a mechanism by which NGA-CNPs sensitize cancer cells to the effects of radiation (Figure 8). However, additional studies are needed to determine the relationship between the induction of autophagy and the increased rate of cell death.

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