The pro-social neurohormone oxytocin reverses the actions of the stress hormone cortisol in human ovarian carcinoma cells in vitro

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.

Oxytocin and cancer: An emerging link

“…This team of investigators, therefore, proposed that a system involving P-LAP and oxytocin plays a role in the regulation of human endometrial adenocarcinoma, in which P-LAP exerts a functionally positive impact on carcinoma cell growth by degrading suppressive peptides such as oxytocin. More recently, these effects have also been linked with a cross-talk network between oxytocin and the stress hormone cortisol, whereby oxytocin reversed the carcinogenic effects of cortisol via autophagy (cellular self-degradation)[ 71 ]. Interestingly, pertinent to the postulated connection between oxytocin and symptoms of autism[ 39 ], oxytocin and cancer have also demonstrated an inverse relationship in autistic children[ 72 ].…”

“…For example, instead of being increased as a direct response to exercise, oxytocin may be induced to assist its “companion” hormone, vasopressin, a well-known hormonal regulator of body fluid homeostasis[ 97 ]. Cortisol, the “stress hormone” and the rhythm surrounding its release has been linked to the progression and survival from various cancers[ 98 - 101 ], and has also been linked to oxytocin[ 71 , 72 ]. The ability to completely elucidate various pathways and mechanisms of actions would go a long way to showing if the established connection between the different hormones extends to cancer.…”

Oxytocin inhibits ovarian cancer metastasis by repressing the expression of MMP-2 and VEGF

“…Therefore, we speculate that the activation of OXTRs inhibits the progression of ovarian cancer. Although OXT inhibited the proliferation, migration and invasion of ovarian cancer as reported 8 , 9 , its underlying mechanisms had not fully elucidated. Morita et al found that OXT inhibited the proliferation, migration and invasion of ovarian cancer by enhancing the expression of E-cadherin and slightly inhibiting MMP-2 in cultured SKOV3 cells 8 .…”

“…Morita et al found that OXT inhibited the proliferation, migration and invasion of ovarian cancer by enhancing the expression of E-cadherin and slightly inhibiting MMP-2 in cultured SKOV3 cells 8 . Mankarious et al revealed that OXT induced apoptosis in cultured three ovarian cancer cell lines including SKOV3, MDAH-2774 and PEO1 9 . Here we first reported that OXT suppressed the ovarian cancer metastasis by repressing not only the expression of MMP-2, but also angiogenesis in cultured A2780 cells.…”

Análise cienciométrica sobre a relação da vivência de eventos de vida produtores de estresse e desenvolvimento de câncer

“…6,7 A secreção crônica de cortisol, em resposta a eventos estressores, tem sido associada com o desenvolvimento de patologias diversas como: doença cardíaca coronoriana, 4 osteoporose, 8 úlcera de membros inferiores 9 e recentemente há um crescente número de estudos que apontam uma correlação positiva entre aumentos crônicos dos níveis plasmáticos de cortisol induzido por estresse e desenvolvimento de neoplasias. [10][11][12][13] Tentativas de associar a etiologia das neoplasias malignas com os eventos estressantes diários datam desde a Grécia antiga, onde Galeno sugeria que mulheres melancólicas e depressivas eram mais propensas a desenvolver o câncer do que aquelas com um alto astral. 6 Embora até então muitos estudos tenham sido realizados neste âmbito, ainda não há um consenso quanto à influência dos eventos estressores diários no desenvolvimento de neoplasias.…”