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Melatonin Induces Oxidative Stress in Placental Human Choriocarcinoma Cells.

Kharrat, Fatma; Vaillancourt, Cathy . Melatonin Induces Oxidative Stress in Placental Human Choriocarcinoma Cells. In: 66th Annual Scientific Meeting of the Society of Reproductive Investigation, 12-16 mars 2019, Paris, France.

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Résumé

Introduction: Melatonin is produced by placental trophoblastic cells which express its receptors. This indolamine acts as a powerful antioxidant preventing oxidative stress-induced damages in cytotrophoblasts. However, in choriocarcinoma cells, it promotes cell death by apoptosis. The mechanism behind this action is yet unknown. We hypothesize that melatonin increases oxidative stress in choriocarcinoma cells to stimulate intrinsic apoptosis. We aim to study the effect of increasing melatonin concentrations (0-1mM) on oxidative stress levels and its major hallmarks in placental choriocarcinoma cell line (BeWo).

Methods: BeWo cells underwent normoxia (8% O2) or hypoxia (0,5% O2) followed by reoxygenation (8% O2) (H/R), with or without melatonin (0-1mM). We first measured Reactive Oxygen Species (ROS) levels with the general oxidative stress indicator Carboxy-H2DCFDA. Then, we studied the expression of pro-oxidant (Xanthine Oxidase (XO)) and anti-oxidant (Superoxide Dismutases (SODs), glutathione peroxidase (GPx) and catalase (CAT)) enzymes using Western-blot. Last, we investigated the effect of melatonin on lipid peroxidation with Thiobarbituric Assay Test (TBARS) and protein carbonyl content by fluorimetry.

Results: Results showed a significant increase of ROS levels in BeWo cells under normoxia (P ≤ 0,01) and under H/R (P ≤ 0,1) at 1mM melatonin concentration. The main ROS generator, XO, demonstrated an increased expression with melatonin in normoxic condition, just as SODs (1nM; P ≤ 0,05), GPx (1μM; P ≤ 0,05) and CAT (1μM; P ≤ 0,05) expressions, miming H/R effect. Treating with different melatonin concentrations resulted also in an increase of lipid peroxidation and protein carbonylation levels in BeWo cells under normoxia. However, this increase was not detected in H/R condition, where melatonin seemed not having any effect on none of the tests.

Conclusion: Our data confirmed that melatonin increases oxidative stress and its major hallmarks in tumoral choriocarcinoma cells. Nevertheless, further research is needed to elucidate its exact anti-tumoral mechanism of action in placental cancer.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Reproductive Sciences (2019), 26 (suppl.1), A170 Affiche scientifique
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 22 nov. 2019 06:14
Dernière modification: 22 nov. 2019 06:14
URI: http://espace.inrs.ca/id/eprint/8206

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