Please use this identifier to cite or link to this item: http://buratest.brunel.ac.uk/handle/2438/12309
Title: The pro-social neurohormone oxytocin reverses the actions of the stress hormone cortisol in human ovarian carcinoma cells in vitro
Authors: Mankarious, A
Dave, F
Pados, G
Tsolakidis, D
Gidron, Y
Pang, Y
Thomas, P
Hall, M
Karteris, E
Keywords: Ovarian cancer;Oxytocin;Cortisol;Glucocorticoid receptors
Issue Date: 2016
Publisher: Spandidos Publications
Citation: International Journal of Oncology, 48: pp.1805-1814, (2016)
Abstract: The journey patients with ovarian cancer travel from non-specific symptoms causing delayed diagnosis through surgery and chemotherapy, culminating in a 5-year survival rate of 43%, must have a profound and detrimental psychological impact on patients. Emerging studies link higher levels of oxytocin (OT) and increased social support, an independent prognostic factor in cancer, with a moderating effect on stress. In contrast, there is a known association of tumour cell proliferation with elevated cortisol (stress hormone) levels. We hypothesise therefore that there is cross-talk between cortisol and oxytocin at a molecular level. Three ovarian cancer cell lines, used as in vitro models, were treated with cortisol at concentrations mimicking physiological stress in vivo in the presence or absence of OT. OT reduced cell proliferation and migration, induced apoptosis and autophagy for all three cell lines, partially reversing the effects of cortisol. Quantitative RT-PCR of tissue taken from ovarian cancer patients revealed that the glucocorticoid receptor (splice variant GR-P) and OT receptor (OTR) were significantly upregulated compared to controls. Tissue microarray revealed that the expression of GRα was lower in the ovarian cancer samples compared to normal tissue. OT is also shown to drive alternative splicing of the GR gene and cortisol-induced OTR expression. OT was able to transactivate GR in the presence of cortisol thus providing further evidence of cross-talk in vitro. These data provide explanations for why social support might help distressed ovarian cancer patients and help define novel hypotheses regarding potential therapeutic interventions in socially isolated patients.
URI: http://www.spandidos-publications.com/10.3892/ijo.2016.3410
http://bura.brunel.ac.uk/handle/2438/12309
DOI: http://doi.dx.org/10.3892/ijo.2016.3410
ISSN: 1791-2423
Appears in Collections:Dept of Life Sciences Research Papers

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