Ex Vivo treatment of coronary artery endothelial cells with serum post-exercise training offers limited protection against in vitro exposure to FEC-T chemotherapy

Marie Mclaughlin; Katie L Hesketh; Sarah L Horgan; Geraint Florida-James; Matthew Cocks; Juliette A Strauss; Mark Ross

doi:10.3389/fphys.2023.1079983

Ex Vivo treatment of coronary artery endothelial cells with serum post-exercise training offers limited protection against in vitro exposure to FEC-T chemotherapy

Front Physiol. 2023 Feb 2:14:1079983. doi: 10.3389/fphys.2023.1079983. eCollection 2023.

Authors

Marie Mclaughlin^{1

2}, Katie L Hesketh³, Sarah L Horgan¹, Geraint Florida-James¹, Matthew Cocks³, Juliette A Strauss³, Mark Ross^{1

4}

Affiliations

¹ School of Applied Sciences, Edinburgh Napier University, Edinburgh, United Kingdom.
² School of Health and Life Sciences, University of the West of Scotland, Lanarkshire, United Kingdom.
³ Liverpool John Moores University, School of Sport and Exercise Sciences, Liverpool, United Kingdom.
⁴ School of Energy, Geoscience, Infrastructure and Society, Heriot Watt University, Edinburgh, United Kingdom.

Abstract

Background: Chemotherapy treatment for breast cancer associates with well-documented cardiovascular detriments. Exercise has shown promise as a potentially protective intervention against cardiac toxicity. However, there is a paucity of evidence for the benefits of exercise on the vasculature. Objectives: This study aimed to determine the effects of chemotherapy on the vascular endothelium; and if there are protective effects of serological alterations elicited by an exercise training intervention. Methods and Results: 15 women participated in a 12-week home-based exercise intervention consisting of three high-intensity interval sessions per week. Human coronary artery endothelial cells (HCAEC) were exposed to physiological concentrations of 5-fluorouracil, epirubicin, cyclophosphamide (FEC) and docetaxel to determine a dose-response. Twenty-4 hours prior to FEC and docetaxel exposure, HCAECs were preconditioned with serum collected pre- and post-training. Annexin V binding and cleaved caspase-3 were assessed using flow cytometry and wound repair by scratch assays. Chemotherapy exposure increased HCAEC Annexin V binding, cleaved caspase-3 expression in a dose-dependent manner; and inhibited wound repair. Compared to pre-training serum, conditioning HCAECs with post-training serum, reduced Annexin V binding (42% vs. 30%, p = 0.01) when exposed to FEC. For docetaxel, there were no within-group differences (pre-vs post-exercise) for Annexin V binding or cleaved caspase-3 expression. There was a protective effect of post-training serum on wound repair for 5-flurouracil (p = 0.03) only. Conclusion: FEC-T chemotherapy drugs cause significant damage and dysfunction of endothelial cells. Preconditioning with serum collected after an exercise training intervention, elicited some protection against the usual toxicity of FEC-T, when compared to control serum.

Keywords: apoptosis; cancer; chemotherapy; endothelium; exercise; wound healing.

Grants and funding

This study was funded by the Peter KK Lee PhD Studentship at Edinburgh Napier University. The exercise intervention was funded by Buckinghamshire Healthcare NHS Trust, awarded to MC, Liverpool John Moores University.