Catecholamine‐Induced DNA Damage in Ovarian Cancer Cells

Abstract

Ovarian cancer is the fifth leading cause of mortality among women, responsible for 5% of all cancer deaths in women in the USA. Remarkable evidence exists of the relationship between the activation of the sympathetic nervous system and cancer progression. Interestingly, recent data suggest that adrenergic signaling alters genetic integrity of cancer cells by damaging the DNA and/or influencing the DNA Damage Response and Repair pathways. In addition, previous data suggest that increased adrenergic stimulation from stress released catecholamines can lead to genomic instability in various in vitro models. Therefore, we hypothesized that increased adrenergic activity will induce DNA damage in ovarian cancer cell lines. To test this, ovarian cancer cells were exposed to catecholamines (epinephrine and norepinephrine) for 1h and 24h; then, double‐stranded damaged was assessed by Neutral Comet Assays and γH2AX foci formation. Results show that norepinephrine significantly increased foci formation and induced higher levels of double‐stranded DNA breaks in SKOV3, OV90 and COV362 cells when compared to control group. Lastly, to determine if DNA damage is due to adrenergic stimuli, cells were pretreated with propranolol (non‐specific β‐blocker) and results showed a significant reduction in DNA damage levels. These results suggest that catecholamines can induce double‐stranded DNA damage in ovarian cancer cells.