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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

Effect of NGA-CNPs on MCF-7 cell cycle distribution.Notes: (A) Cells were pretreated with the vehicle DMSO or NGA-CNPs for 24 hours before exposure to 0 Gy or 6 Gy radiation, and the fraction of cells in each phase of the cell cycle was analyzed by flow cytometry. (B) Quantitative analysis of cell cycle distribution.Abbreviations: NGA-CNP, ceria nanoparticle modified with neogambogic acid; DMSO, dimethyl sulfoxide; G2, second gap phase; M, mitosis phase; S, synthesis phase; G0, zero gap phase; G1, first gap phase.
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f6-ijn-10-4957: Effect of NGA-CNPs on MCF-7 cell cycle distribution.Notes: (A) Cells were pretreated with the vehicle DMSO or NGA-CNPs for 24 hours before exposure to 0 Gy or 6 Gy radiation, and the fraction of cells in each phase of the cell cycle was analyzed by flow cytometry. (B) Quantitative analysis of cell cycle distribution.Abbreviations: NGA-CNP, ceria nanoparticle modified with neogambogic acid; DMSO, dimethyl sulfoxide; G2, second gap phase; M, mitosis phase; S, synthesis phase; G0, zero gap phase; G1, first gap phase.

Mentions: To clarify the mechanism by which NGA-CNPs enhance cancer cell sensitivity to radiation, we examined the effects of combined treatment on cell cycle regulation by flow cytometry. Treatment with NGA-CNPs and radiation decreased the fraction of cells in G0/G1 phase and increased the fraction in G2/M phase as compared to untreated control cells (Figure 6). For instance, 4.57% of control cells were in G2/M phase; NGA-CNP treatment at concentrations of 10 μg/mL and 20 μg/mL increased the G2/M fraction to 4.89% and 6.44%, respectively; these values increased to 17.39% and 18.03%, respectively (P<0.05 vs 6 Gy radiation only), when NGA-CNPs were combined with 6 Gy radiation. These results indicate that simultaneous exposure of cells to NGA-CNPs and radiation causes acceleration through G1/S and arrest in G2/M phase. Since cells are most sensitive to the effects of radiation in the latter phase and most resistant in G0/G1,33 one potential mechanism by which NGA-CNPs enhance the effects of radiotherapy is by regulating cell cycle progression.


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)

Effect of NGA-CNPs on MCF-7 cell cycle distribution.Notes: (A) Cells were pretreated with the vehicle DMSO or NGA-CNPs for 24 hours before exposure to 0 Gy or 6 Gy radiation, and the fraction of cells in each phase of the cell cycle was analyzed by flow cytometry. (B) Quantitative analysis of cell cycle distribution.Abbreviations: NGA-CNP, ceria nanoparticle modified with neogambogic acid; DMSO, dimethyl sulfoxide; G2, second gap phase; M, mitosis phase; S, synthesis phase; G0, zero gap phase; G1, first gap phase.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4542556&req=5

f6-ijn-10-4957: Effect of NGA-CNPs on MCF-7 cell cycle distribution.Notes: (A) Cells were pretreated with the vehicle DMSO or NGA-CNPs for 24 hours before exposure to 0 Gy or 6 Gy radiation, and the fraction of cells in each phase of the cell cycle was analyzed by flow cytometry. (B) Quantitative analysis of cell cycle distribution.Abbreviations: NGA-CNP, ceria nanoparticle modified with neogambogic acid; DMSO, dimethyl sulfoxide; G2, second gap phase; M, mitosis phase; S, synthesis phase; G0, zero gap phase; G1, first gap phase.
Mentions: To clarify the mechanism by which NGA-CNPs enhance cancer cell sensitivity to radiation, we examined the effects of combined treatment on cell cycle regulation by flow cytometry. Treatment with NGA-CNPs and radiation decreased the fraction of cells in G0/G1 phase and increased the fraction in G2/M phase as compared to untreated control cells (Figure 6). For instance, 4.57% of control cells were in G2/M phase; NGA-CNP treatment at concentrations of 10 μg/mL and 20 μg/mL increased the G2/M fraction to 4.89% and 6.44%, respectively; these values increased to 17.39% and 18.03%, respectively (P<0.05 vs 6 Gy radiation only), when NGA-CNPs were combined with 6 Gy radiation. These results indicate that simultaneous exposure of cells to NGA-CNPs and radiation causes acceleration through G1/S and arrest in G2/M phase. Since cells are most sensitive to the effects of radiation in the latter phase and most resistant in G0/G1,33 one potential mechanism by which NGA-CNPs enhance the effects of radiotherapy is by regulating cell cycle progression.

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