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


In this work, untargeted metabolomics was used to unveil the impact of a Eucalyptus (Eucalyptus nitens) outer bark lipophilic extract on the metabolism of triple negative breast cancer (TNBC) and nontumor breast cells. Integrative analysis of culture medium, intracellular polar metabolites, and cellular lipids provided a comprehensive picture of cell 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 48 h incubation with the E. nitens extract (15 mu g/mL), was the enhancement of the NAD(+)/NADH ratio, likely reflecting a shift to mitochondrial respiration, which appeared to be fueled 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 tricarboxylic acid cycle (resulting in a decreased NAD(+)/NADH ratio), while having no effect on the cell lipid composition. This knowledge improves the 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.



subject category

Biochemical Research Methods


Guerra, AR; Soares, BIG; Freire, CSR; Silvestre, AJD; Duarte, MF; Duarte, IF

our authors


This work was developed within the scope of the projects CICECO-Aveiro Institute of Materials (UIDB/50011/2020 & UIDP/50011/2020) and MED-Mediterranean Institute for Agriculture, Environment and Development (UIDB/05183/2020), financed by national funds through the Foundation for Science and Technology/MCTES, Portugal. Funding to the project NEucBark.New valorization strategies for Eucalyptus spp. Bark Extracts (PTDC/AGR-FOR/3187/2012) by FEDER through COMPETE and by national funds through FCT is also acknowledged. The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure project no. 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). A. R.G. acknowledges the FCT awarded grant SFRH/BD/98635/2013.

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