Norepinephrine-Induced DNA Damage in Ovarian Cancer Cells

• Published in: International journal of molecular sciences Vol. 21; no. 6; p. 2250
• Main Authors: Lamboy-Caraballo, Rocio, Ortiz-Sanchez, Carmen, Acevedo-Santiago, Arelis, Matta, Jaime, N.A. Monteiro, Alvaro, N. Armaiz-Pena, Guillermo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.03.2020; MDPI
• Subjects: Catecholamines; Cell Line, Tumor; Cisplatin - pharmacology; Deoxyribonucleic acid; DNA; DNA Breaks, Double-Stranded - drug effects; DNA damage; DNA repair; Epinephrine - pharmacology; Female; Histones - metabolism; Humans; Mutation; Norepinephrine - pharmacology; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Stress; norepinephrine; stress; ovarian cancer; adrenergic receptors; DNA lesions; epinephrine; cisplatin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21062250

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.