Abstract 37P
Background
Ovarian cancer (OC) grows rapidly and one of the features associated with its aggressivenes rely on the glycolytic metabolism; unsuccessfully, therapeutic targeting of glycolysis has failed due to the lack of selective, effective and safe inhibitors. Melatonin is an indolamine that display a number of anti-tumor effects via different mechanisms that are dependent or independent of its receptors MT1 and MT2. We therefore evaluated the role of melatonin in reversing the Warburg effect in human OC cells and if the actions are MT1/2 mediated.
Methods
We treated OC SKOV-3 cells, possessing intact or silenced MT1/2 by siRNA, with increasing doses of melatonin (1600, 3200 and 4000μM after 48h exposure) and measured the migration rate and apoptosis by flow citometry. We further analyzed glucose consumption, lactate release and lactate dehydrogenase (LDH) activity through functional assays.
Results
Cell viability was reduced after melatonin exposure regardless the presence of MT1/2 and only the highest dose of 4000 μM attenuated the migration rate; conversely, the silenced cells showed a dramatic reduction in migration (<25% versus control). Apoptosis rate was increased in a dose-dependent manner after melatonin treatment; necrosis was higher following the higher doses of 3200 μM e 4000 μM. Q glucose consumption was decreased after 4000 μM melatonin in contrast to an elevation after MT1/2 knockdown. OC cells showed lower Q lactate releasing after treatment with 3200 μM melatonin while MT1/2 knockdown had an opposite effect; LDH activity was reduced in the presence of MT1/2 rather than increased in silenced cells after treatment with higher doses of melatonin.
Conclusions
Melatonin decreased the migratory potential of ovarian cancer cells in addition to inducing apoptosis regardless of the presence of MT1/2 receptors. These effects are partially attributted to the reversion of glycolytic phenotype of OC cells through binding of melatonin to the MT1/2 receptors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Institute of Biosciences of Botucatu.
Funding
FAPESP (grant number: 2019/00906-6, 2018/15797-5).
Disclosure
All authors have declared no conflicts of interest.