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.
N1 - Funding Information:
National Institutes of Health RO1 grant CA12587-06 awarded to Steven R. Buchman, M.D., supported this work.
Publisher Copyright:
© 2019 by the American Society of Plastic Surgeons
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..
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..
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
SN - 0032-1052
VL - 143
SP - 1666
EP - 1676
JO - Plastic and reconstructive surgery
JF - Plastic and reconstructive surgery
IS - 6
ER -