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Open AccessArticle

Norepinephrine-Induced DNA Damage in Ovarian Cancer Cells

1
Department of Basic Sciences, Division of Pharmacology, School of Medicine, Ponce Health Sciences University, Ponce, PR 00716, USA
2
Division of Cancer Biology, Ponce Research Institute, Ponce, PR 00716, USA
3
Biomedical Sciences Program, University of Puerto Rico, Ponce, PR 00716, USA
4
Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
5
Division of Women’s Health, Ponce Research Institute, Ponce, PR 00716, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(6), 2250; https://doi.org/10.3390/ijms21062250
Received: 27 February 2020 / Revised: 18 March 2020 / Accepted: 20 March 2020 / Published: 24 March 2020
(This article belongs to the Special Issue Recognition of DNA Lesions)
Multiple studies have shown that psychological distress in epithelial ovarian cancer (EOC) patients is associated with worse quality of life and poor treatment adherence. This may influence chemotherapy response and prognosis. Moreover, although stress hormones can reduce cisplatin efficacy in EOC treatment, their effect on the integrity of DNA remains poorly understood. In this study, we investigated whether norepinephrine and epinephrine can induce DNA damage and modulate cisplatin-induced DNA damage in three EOC cell lines. Our data show that norepinephrine and epinephrine exposure led to increased nuclear γ-H2AX foci formation in EOC cells, a marker of double-strand DNA breaks. We further characterized norepinephrine-induced DNA damage by subjecting EOC cells to alkaline and neutral comet assays. Norepinephrine exposure caused DNA double-strand breaks, but not single-strand breaks. Interestingly, pre-treatment with propranolol abrogated norepinephrine-induced DNA damage indicating that its effects may be mediated by β-adrenergic receptors. Lastly, we determined the effects of norepinephrine on cisplatin-induced DNA damage. Our data suggest that norepinephrine reduced cisplatin-induced DNA damage in EOC cells and that this effect may be mediated independently of β-adrenergic receptors. Taken together, these results suggest that stress hormones can affect DNA integrity and modulate cisplatin resistance in EOC cells. View Full-Text
Keywords: norepinephrine; epinephrine; stress; adrenergic receptors; ovarian cancer; DNA lesions; cisplatin norepinephrine; epinephrine; stress; adrenergic receptors; ovarian cancer; DNA lesions; cisplatin
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Lamboy-Caraballo, R.; Ortiz-Sanchez, C.; Acevedo-Santiago, A.; Matta, J.; N.A. Monteiro, A.; N. Armaiz-Pena, G. Norepinephrine-Induced DNA Damage in Ovarian Cancer Cells. Int. J. Mol. Sci. 2020, 21, 2250.

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