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Hypoxia and Cellular Localization Influence the Radiosensitizing Effect of Gold Nanoparticles (AuNPs) in Breast Cancer Cells

by Tse, Kenneth , Zafarana, Gaetano , Bristow, Robert G. , Cui, Lei , Allen, Christine , Jaffray, David A. , Harding, Shane M. , Zahedi, Payam

in Breast Neoplasms - pathology / Breast Neoplasms - radiotherapy / Cancer / Cell Cycle - drug effects / Cell Hypoxia / Cell Line, Tumor / Cellular / Deoxyribonucleic acid / DNA / DNA Breaks, Double-Stranded / Female / Gold / Gold - pharmacology / Humans / Hypoxia / Localization / Metal Nanoparticles - administration & dosage / Nanoparticles / Position (location) / Rad51 Recombinase - analysis / Radiation-Sensitizing Agents - pharmacology / Reactive Oxygen Species - metabolism / REGULAR ARTICLES / Repair

2014

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Hypoxia and Cellular Localization Influence the Radiosensitizing Effect of Gold Nanoparticles (AuNPs) in Breast Cancer Cells

by Tse, Kenneth , Zafarana, Gaetano , Bristow, Robert G. , Cui, Lei , Allen, Christine , Jaffray, David A. , Harding, Shane M. , Zahedi, Payam

2014

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Hypoxia and Cellular Localization Influence the Radiosensitizing Effect of Gold Nanoparticles (AuNPs) in Breast Cancer Cells

by Tse, Kenneth , Zafarana, Gaetano , Bristow, Robert G. , Cui, Lei , Allen, Christine , Jaffray, David A. , Harding, Shane M. , Zahedi, Payam

2014

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Journal Article

Hypoxia and Cellular Localization Influence the Radiosensitizing Effect of Gold Nanoparticles (AuNPs) in Breast Cancer Cells

Tse, Kenneth,

Zafarana, Gaetano,

Bristow, Robert G.,

Cui, Lei,

Allen, Christine,

Jaffray, David A.,

Harding, Shane M.,

Zahedi, Payam

2014

Overview

Hypoxia exists in all solid tumors and leads to clinical radioresistance and adverse prognosis. We hypothesized that hypoxia and cellular localization of gold nanoparticles (AuNPs) could be modifiers of AuNP-mediated radiosensitization. The possible mechanistic effect of AuNPs on cell cycle distribution and DNA double-strand break (DSB) repair postirradiation were also studied. Clonogenic survival data revealed that internalized and extracellular AuNPs at 0.5 mg/mL resulted in dose enhancement factors of 1.39 ± 0.07 and 1.09 ± 0.01, respectively. Radiosensitization by AuNPs was greatest in cells under oxia, followed by chronic and then acute hypoxia. The presence of AuNPs inhibited postirradiation DNA DSB repair, but did not lead to cell cycle synchronization. The relative radiosensitivity of chronic hypoxic cells is attributed to defective DSB repair (homologous recombination) due to decreased (RAD51)-associated protein expression. Our results support the need for further study of AuNPs for clinical development in cancer therapy since their efficacy is not limited in chronic hypoxic cells.

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Publisher

The Radiation Research Society,Radiation Research Society,Allen Press Inc

Subject

Breast Neoplasms - pathology

/ Breast Neoplasms - radiotherapy

/ Cancer

/ Cell Cycle - drug effects

/ Cell Hypoxia

/ Cell Line, Tumor

/ Cellular