abstract
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.
keywords
OUTER BARKS; MITOCHONDRIAL; TARGET; GROWTH; ER
subject category
Biochemical Research Methods
authors
Guerra, AR; Soares, BIG; Freire, CSR; Silvestre, AJD; Duarte, MF; Duarte, IF
our authors
Ângela Guerra
PhD Student
Armando Jorge Domingues Silvestre
Full professor
Belinda Soares
PhD Student
Carmen Sofia da Rocha Freire Barros
Coordinating Researcher
Iola Melissa Fernandes Duarte
Principal Researcher
Maria de Fátima Pereira Duarte
Principal ResearcherGroups
G4 - Renewable Materials and Circular Economy
G5 - Biomimetic, Biological and Living Materials
Projects
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Eucalyptus triterpenic biological activity (PTDC/AGR-FOR/3187/2012)
acknowledgements
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.