Metabolic Effects of a Eucalyptus Bark Lipophilic Extract on Triple Negative Breast Cancer and Non-Tumor Breast Epithelial Cells

In this work, untargeted metabolomics was used to unveil the impact of a Eucalyptus (E. nitens) lipophilic outer bark extract on the metabolism of triple negative breast cancer (TNBC) and non-tumour breast cells. Integrative analysis of culture medium, intracellular polar metabolites and cellular lipids provided a comprehensive picture of cells metabolic adaptations, which enabled several hypotheses about the metabolic targets and pathways affected to be proposed. One of the most marked effects in MDA-MB-231 breast cancer cells, upon 48h incubation with the E. nitens extract (15 µg/mL), comprised enhancement of the NAD+/NADH ratio, likely reflecting a shift to mitochondrial respiration, which appeared to be fuelled by amino acids and fatty acids resulting from hydrolysis of neutral lipids (triglycerides and cholesteryl esters). Contrastingly, in MCF-10A breast epithelial cells, the E. nitens extract appeared to intensify glycolysis and the TCA cycle (resulting in decreased NAD+/NADH ratio) and had no effect on the cells lipid composition. This knowledge contributes to improve current understanding of the biological activity of E. nitens bark extracts, and is potentially useful to promote their development in the field of TNBC anticancer therapy.