Publication
Cardiac molecular remodeling by anticancer drugs: Doxorubicin affects more metabolism while mitoxantrone impacts more autophagy in adult CD-1 male mice
| dc.contributor.author | Brandão, Sofia Reis | |
| dc.contributor.author | Reis-Mendes, Ana | |
| dc.contributor.author | Duarte-Araújo, Margarida | |
| dc.contributor.author | Neuparth, Maria João | |
| dc.contributor.author | Rocha, Hugo | |
| dc.contributor.author | Carvalho, Félix | |
| dc.contributor.author | Ferreira, Rita | |
| dc.contributor.author | Costa, Vera Marisa | |
| dc.date.accessioned | 2024-03-18T15:53:13Z | |
| dc.date.available | 2024-03-18T15:53:13Z | |
| dc.date.issued | 2023-05-31 | |
| dc.description.abstract | Doxorubicin (DOX) and mitoxantrone (MTX) are classical chemotherapeutic agents used in cancer that induce similar clinical cardiotoxic effects, although it is not clear if they share similar underlying molecular mechanisms. We aimed to assess the effects of DOX and MTX on the cardiac remodeling, focusing mainly on metabolism and autophagy. Adult male CD-1 mice received pharmacologically relevant cumulative doses of DOX (18 mg/kg) and MTX (6 mg/kg). Both DOX and MTX disturbed cardiac metabolism, decreasing glycolysis, and increasing the dependency on fatty acids (FA) oxidation, namely, through decreased AMP-activated protein kinase (AMPK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) content and decreased free carnitine (C0) and increased acetylcarnitine (C2) concentration. Additionally, DOX heavily influenced glycolysis, oxidative metabolism, and amino acids turnover by exclusively decreasing phosphofructokinase (PFKM) and electron transfer flavoprotein-ubiquinone oxidoreductase (ETFDH) content, and the concentration of several amino acids. Conversely, both drugs downregulated autophagy given by the decreased content of autophagy protein 5 (ATG5) and microtubule-associated protein light chain 3 (LC3B), with MTX having also an impact on Beclin1. These results emphasize that DOX and MTX modulate cardiac remodeling differently, despite their clinical similarities, which is of paramount importance for future treatments. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Brandão, S. R., Reis-Mendes, A., Duarte-Araújo, M., Neuparth, M. J., Rocha, H., Carvalho, F., Ferreira, R., & Costa, V. M. (2023). Cardiac molecular remodeling by anticancer drugs: Doxorubicin affects more metabolism while Mitoxantrone impacts more autophagy in adult CD-1 male mice. Biomolecules, 13(6), Artigo 6. https://doi.org/10.3390/biom13060921 | pt_PT |
| dc.identifier.doi | 10.3390/biom13060921 | pt_PT |
| dc.identifier.eissn | 2218-273X | |
| dc.identifier.uri | http://hdl.handle.net/10400.22/25185 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | MDPI | pt_PT |
| dc.relation | This research was funded by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the projects UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences – UCIBIO, the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB, the project UIDB/50006/2020 of the LAQV-REQUIMTE Aveiro, the project UIDB/00617/2020 of the CIAFEL, the project LA/P/0064/2020 of the ITR—Laboratory for Integrative and Translational Research in Population Health. S.R.B., A.R.M., and V.M.C. acknowledge FCT and European Social Fund (FSE) for their grants (SFRH/BD/138202/2018, SFRH/BD/129359/2017, and SFRH/BPD/110001/2015). VMC grant was given under Norma Transitória DL57/2016/CP1334/CT0006. | pt_PT |
| dc.relation.publisherversion | https://doi.org/10.3390/biom13060921 | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt_PT |
| dc.subject | Cardiotoxicity | pt_PT |
| dc.subject | Anticancer agents | pt_PT |
| dc.subject | Molecular mechanisms | pt_PT |
| dc.subject | Mitochondrial dynamics | pt_PT |
| dc.title | Cardiac molecular remodeling by anticancer drugs: Doxorubicin affects more metabolism while mitoxantrone impacts more autophagy in adult CD-1 male mice | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 22 | pt_PT |
| oaire.citation.startPage | 1 | pt_PT |
| oaire.citation.title | Biomolecules | pt_PT |
| oaire.citation.volume | 13(6) | pt_PT |
| person.familyName | Carvalho de Azevedo Rocha | |
| person.givenName | Hugo Daniel | |
| person.identifier.ciencia-id | 331F-6236-B34F | |
| person.identifier.orcid | 0000-0001-5447-615X | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isAuthorOfPublication | a67d8ec6-bfd4-415f-9615-8d8c8a48166e | |
| relation.isAuthorOfPublication.latestForDiscovery | a67d8ec6-bfd4-415f-9615-8d8c8a48166e |