The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety

Jeremy V. Lynn, Kevin M. Urlaub, Kavitha Ranganathan, Alexis Donneys, Noah S. Nelson, Chitra Subramanian, Mark S. Cohen, Steven R. Buchman

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine has immense potential to up-regulate angiogenesis and improve reconstructive outcomes. The purpose of this study was to determine the impact of deferoxamine on breast cancer cell proliferation in vitro, to delineate oncologic safety concerns regarding the use of deferoxamine as a regenerative therapeutic. METHODS: The dose-dependent effect of radiation and deferoxamine on two triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) was determined by means of MTS (percentage cell viability) and tumorsphere (sphere number) analysis. Radiation therapy and deferoxamine were delivered both individually and in combination, and all experiments were completed in triplicate. Intracellular iron, nuclear factor-κB localization, and apoptosis/necrosis assays were performed to delineate mechanism. Analysis of variance statistical analysis was performed using SPSS (p < 0.05). RESULTS: For both cell lines, percentage viability and sphere number significantly decreased following exposure to 10 Gy of radiation. Surprisingly, the administration of 25 µM deferoxamine also significantly decreased each metric. The administration of deferoxamine (100 µM) in combination with radiation (10 Gy) resulted in significantly reduced percentage viability and sphere number compared with the administration of radiation alone. Deferoxamine treatment decreased intracellular iron, suppressed nuclear factor-κB activation, and induced apoptosis. CONCLUSION: Radiation and deferoxamine significantly decrease breast cancer proliferation when delivered independently and in combination, suggesting deferoxamine may be safely used to facilitate improved reconstructive outcomes among triple-negative breast cancer survivors. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Original languageEnglish (US)
Pages (from-to)1666-1676
Number of pages11
JournalPlastic and reconstructive surgery
Volume143
Issue number6
DOIs
StatePublished - Jun 1 2019
Externally publishedYes

Fingerprint

Deferoxamine
Mammaplasty
Safety
Triple Negative Breast Neoplasms
Radiation Dosage
Radiotherapy
Breast Neoplasms
Analysis of Variance
Iron
Radiation
Apoptosis
Cell Line
Radiation Effects
Cell Survival
Necrosis
Up-Regulation
Therapeutics
Cell Proliferation

ASJC Scopus subject areas

  • Surgery

Cite this

Lynn, J. V., Urlaub, K. M., Ranganathan, K., Donneys, A., Nelson, N. S., Subramanian, C., ... Buchman, S. R. (2019). The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety. Plastic and reconstructive surgery, 143(6), 1666-1676. https://doi.org/10.1097/PRS.0000000000005647

The Role of Deferoxamine in Irradiated Breast Reconstruction : A Study of Oncologic Safety. / Lynn, Jeremy V.; Urlaub, Kevin M.; Ranganathan, Kavitha; Donneys, Alexis; Nelson, Noah S.; Subramanian, Chitra; Cohen, Mark S.; Buchman, Steven R.

In: Plastic and reconstructive surgery, Vol. 143, No. 6, 01.06.2019, p. 1666-1676.

Research output: Contribution to journalArticle

Lynn, JV, Urlaub, KM, Ranganathan, K, Donneys, A, Nelson, NS, Subramanian, C, Cohen, MS & Buchman, SR 2019, 'The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety', Plastic and reconstructive surgery, vol. 143, no. 6, pp. 1666-1676. https://doi.org/10.1097/PRS.0000000000005647
Lynn, Jeremy V. ; Urlaub, Kevin M. ; Ranganathan, Kavitha ; Donneys, Alexis ; Nelson, Noah S. ; Subramanian, Chitra ; Cohen, Mark S. ; Buchman, Steven R. / The Role of Deferoxamine in Irradiated Breast Reconstruction : A Study of Oncologic Safety. In: Plastic and reconstructive surgery. 2019 ; Vol. 143, No. 6. pp. 1666-1676.
@article{52d9868868a8421fb7d90368644bb6d0,
title = "The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety",
abstract = "BACKGROUND: Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine has immense potential to up-regulate angiogenesis and improve reconstructive outcomes. The purpose of this study was to determine the impact of deferoxamine on breast cancer cell proliferation in vitro, to delineate oncologic safety concerns regarding the use of deferoxamine as a regenerative therapeutic. METHODS: The dose-dependent effect of radiation and deferoxamine on two triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) was determined by means of MTS (percentage cell viability) and tumorsphere (sphere number) analysis. Radiation therapy and deferoxamine were delivered both individually and in combination, and all experiments were completed in triplicate. Intracellular iron, nuclear factor-κB localization, and apoptosis/necrosis assays were performed to delineate mechanism. Analysis of variance statistical analysis was performed using SPSS (p < 0.05). RESULTS: For both cell lines, percentage viability and sphere number significantly decreased following exposure to 10 Gy of radiation. Surprisingly, the administration of 25 µM deferoxamine also significantly decreased each metric. The administration of deferoxamine (100 µM) in combination with radiation (10 Gy) resulted in significantly reduced percentage viability and sphere number compared with the administration of radiation alone. Deferoxamine treatment decreased intracellular iron, suppressed nuclear factor-κB activation, and induced apoptosis. CONCLUSION: Radiation and deferoxamine significantly decrease breast cancer proliferation when delivered independently and in combination, suggesting deferoxamine may be safely used to facilitate improved reconstructive outcomes among triple-negative breast cancer survivors. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.",
author = "Lynn, {Jeremy V.} and Urlaub, {Kevin M.} and Kavitha Ranganathan and Alexis Donneys and Nelson, {Noah S.} and Chitra Subramanian and Cohen, {Mark S.} and Buchman, {Steven R.}",
year = "2019",
month = "6",
day = "1",
doi = "10.1097/PRS.0000000000005647",
language = "English (US)",
volume = "143",
pages = "1666--1676",
journal = "Plastic and Reconstructive Surgery",
issn = "0032-1052",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - The Role of Deferoxamine in Irradiated Breast Reconstruction

T2 - A Study of Oncologic Safety

AU - Lynn, Jeremy V.

AU - Urlaub, Kevin M.

AU - Ranganathan, Kavitha

AU - Donneys, Alexis

AU - Nelson, Noah S.

AU - Subramanian, Chitra

AU - Cohen, Mark S.

AU - Buchman, Steven R.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - BACKGROUND: Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine has immense potential to up-regulate angiogenesis and improve reconstructive outcomes. The purpose of this study was to determine the impact of deferoxamine on breast cancer cell proliferation in vitro, to delineate oncologic safety concerns regarding the use of deferoxamine as a regenerative therapeutic. METHODS: The dose-dependent effect of radiation and deferoxamine on two triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) was determined by means of MTS (percentage cell viability) and tumorsphere (sphere number) analysis. Radiation therapy and deferoxamine were delivered both individually and in combination, and all experiments were completed in triplicate. Intracellular iron, nuclear factor-κB localization, and apoptosis/necrosis assays were performed to delineate mechanism. Analysis of variance statistical analysis was performed using SPSS (p < 0.05). RESULTS: For both cell lines, percentage viability and sphere number significantly decreased following exposure to 10 Gy of radiation. Surprisingly, the administration of 25 µM deferoxamine also significantly decreased each metric. The administration of deferoxamine (100 µM) in combination with radiation (10 Gy) resulted in significantly reduced percentage viability and sphere number compared with the administration of radiation alone. Deferoxamine treatment decreased intracellular iron, suppressed nuclear factor-κB activation, and induced apoptosis. CONCLUSION: Radiation and deferoxamine significantly decrease breast cancer proliferation when delivered independently and in combination, suggesting deferoxamine may be safely used to facilitate improved reconstructive outcomes among triple-negative breast cancer survivors. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

AB - BACKGROUND: Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine has immense potential to up-regulate angiogenesis and improve reconstructive outcomes. The purpose of this study was to determine the impact of deferoxamine on breast cancer cell proliferation in vitro, to delineate oncologic safety concerns regarding the use of deferoxamine as a regenerative therapeutic. METHODS: The dose-dependent effect of radiation and deferoxamine on two triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) was determined by means of MTS (percentage cell viability) and tumorsphere (sphere number) analysis. Radiation therapy and deferoxamine were delivered both individually and in combination, and all experiments were completed in triplicate. Intracellular iron, nuclear factor-κB localization, and apoptosis/necrosis assays were performed to delineate mechanism. Analysis of variance statistical analysis was performed using SPSS (p < 0.05). RESULTS: For both cell lines, percentage viability and sphere number significantly decreased following exposure to 10 Gy of radiation. Surprisingly, the administration of 25 µM deferoxamine also significantly decreased each metric. The administration of deferoxamine (100 µM) in combination with radiation (10 Gy) resulted in significantly reduced percentage viability and sphere number compared with the administration of radiation alone. Deferoxamine treatment decreased intracellular iron, suppressed nuclear factor-κB activation, and induced apoptosis. CONCLUSION: Radiation and deferoxamine significantly decrease breast cancer proliferation when delivered independently and in combination, suggesting deferoxamine may be safely used to facilitate improved reconstructive outcomes among triple-negative breast cancer survivors. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

UR - http://www.scopus.com/inward/record.url?scp=85067266185&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067266185&partnerID=8YFLogxK

U2 - 10.1097/PRS.0000000000005647

DO - 10.1097/PRS.0000000000005647

M3 - Article

C2 - 30907808

AN - SCOPUS:85067266185

VL - 143

SP - 1666

EP - 1676

JO - Plastic and Reconstructive Surgery

JF - Plastic and Reconstructive Surgery

SN - 0032-1052

IS - 6

ER -