Stress hormones induce DNA damage in ovarian cancer cells

Abstract

Activation of the sympathetic nervous system (SNS) is associated with cancer progression. Recent data suggest that adrenergic signaling alters the genetic integrity of cancer cells by damaging the DNA and/or influencing the DNA‐maintenance machinery composed of the DNA Damage Response Pathway and DNA Repair Pathways. Consequently, accumulation of genomic alterations can lead to genomic instability and the acquisition of other cancer hallmarks that drive tumor progression. Still, the exact mechanisms of how sustained adrenergic signaling influences genomic stability is an area that needs to be further studied. We hypothesize that increased adrenergic stimuli will induce significant levels of DNA damage. To assess the extent of DNA damage after catecholamine exposure, we determined p‐H2AX (sensitive marker for double‐stranded DNA damage) expression by western blot and immunofluorescence analyses in SKOV3 and other high‐grade serous ovarian cancer cell lines. Neutral Comet Assays were performed to assess double‐stranded DNA damage after catecholamine exposure. SKOV3 cells that were exposed to epinephrine (Epi) and norepinephrine (Ne) at 1h, 3h, 6h, 12h, and 24h displayed increased expression of p‐H2AX. Moreover, immunofluorescence analyses for p‐H2AX in SKOV3 and OV90 showed increased foci formation (reflecting 1:1 foci/double‐strand break) when compared to the control group. Lastly, Neutral Comet Assay analyses in catecholamine‐treated SKOV3 and COV362 cells displayed higher levels of double‐stranded DNA breaks in comparison to untreated cells. Lastly, to determine if DNA damage is due to adrenergic stimuli, cells were pre‐treated with propranolol (non‐specific β‐blocker) and results showed a significant reduction in the levels of DNA damage. These results suggest that catecholamines can induce double‐stranded DNA damage in ovarian cancer cells.Support or Funding InformationNIMHHD (G12MD007579), NIGMS‐RISE R25GM082406, NCI (U54CA163071 and U54CA163068), U54CA163071‐06, and Ponce Research Institute.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.