Abstract 2504: Melatonin decreases plasma arginine, its precursors and acylcarnitines in breast cancer xenograft model at specific time point during circadian rhythm
Authors: Debora Zuccari, Rubens Paula Junior, Nathália Martins Sonehara, Roger Chammas, Florence Raynaud
Journal: Cancer Research (2017)

Abstract The circadian rhythm regulates the whole metabolism modulating the concentration of various circulating substances through the clear and dark variation. Melatonin is the main mediator of this flow and breast tumors development is linked to imbalance of this rhythm. This hormone has several anti-cancer effects extensively proved by our group. Currently metabolomics analysis have been used in cancer to provide a comprehensive profile of the metabolic changes. Important tumor features are regulated by amino acids likewise fatty acids metabolism. Therefore the comprehension of specific metabolic pathways modulated by melatonin is essencial to verify its useful as adjuvant treatment. The aim of this study was to evaluate the metabolic profile in breast cancer xenograft model treated with melatonin and according the circadian cycle. Were used 160 female Balb/c nude athimic mice divided into four groups: Tumor / Melatonin, Tumor / Vehicle, Non-tumor / Melatonin and Non-tumor / Vehicle. The tumor-bearing animals were developed by implantation of 3x106 triple negative human breast cancer cells (MDA-MB-231) in the mammary fat pad. All the animals received 100 ul of solution by intraperitoneal injection (IP) for five days a week during 21 days. The treated groups received 40 mg/kg of melatonina. Blood sample were collected every 3 hours during 24 hours (eight time points) and the plasma was extracted for analysis by liquid chromatography-mass spectrometry (LC-MS) using the Absolute IDQ p180 Kit (BioCrates). Orthogonal Partial Least Squares (OPLS) analysis showed evident separation of the animals metabolic profile not only because the circadian cycle, but also because the melatonin treatment. We found a significant increasing in arginine and precursors concentration in blood of the tumor-bearing animals specificaly at 6am and 9am. Beside these data we also found alterations in the acylcarnitines levels. The concentrations of medium and long-chain acylcarnitines increased significantly at 3pm. Tumorbearing animals which have been treated with melatonin showed reduced levels of these amino acids and acylcarnitines in blood achieving the same levels of non-tumour bearing animals. In summary ourt work reveals a strong relationship between the metabolic profile and the entire circadian variation as well as the exogenous melatonin can regulates the metabolism. This pre-clinical trial so far unpublished has shown an increase of arginine, its precursors and acylcarnitines at specific time points in the plasma of breast tumor-bearing animals. The treatment with melatonin is capable to deacrese the concentration of these amino acids and acylcarnitines achievning basal levels. Our results corroborate the literature which characterizes these metabolites as biomarkers for cancer and increasingly allow the use of melatonin as an adjuvant therapy for breast cancer. Note: This abstract was not presented at the meeting. Citation Format: Debora Zuccari, Rubens Paula Junior, Nathália Martins Sonehara, Roger Chammas, Florence Raynaud. Melatonin decreases plasma arginine, its precursors and acylcarnitines in breast cancer xenograft model at specific time point during circadian rhythm [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2504. doi:10.1158/1538-7445.AM2017-2504