Frontiers in Pharmacology (Aug 2023)
Acrocomia aculeata associated with doxorubicin: cardioprotection and anticancer activity
- Tamaeh Monteiro-Alfredo,
- Tamaeh Monteiro-Alfredo,
- Tamaeh Monteiro-Alfredo,
- Tamaeh Monteiro-Alfredo,
- Jéssica Maurino dos Santos,
- Kátia Ávila Antunes,
- Janielle Cunha,
- Debora da Silva Baldivia,
- Ana Salomé Pires,
- Ana Salomé Pires,
- Ana Salomé Pires,
- Inês Marques,
- Inês Marques,
- Inês Marques,
- Ana Margarida Abrantes,
- Ana Margarida Abrantes,
- Ana Margarida Abrantes,
- Maria Filomena Botelho,
- Maria Filomena Botelho,
- Maria Filomena Botelho,
- Lúcia Monteiro,
- Ana Cristina Gonçalves,
- Ana Cristina Gonçalves,
- Ana Cristina Gonçalves,
- Wellington Henrique Botelho,
- Ana Paula de Araújo Boleti,
- Célia Cabral,
- Célia Cabral,
- Paulo J. Oliveira,
- Edson Lucas dos Santos,
- Paulo Matafome,
- Paulo Matafome,
- Paulo Matafome,
- Paulo Matafome,
- Kely de Picoli Souza
Affiliations
- Tamaeh Monteiro-Alfredo
- Research Group on Biotechnology and Bioprospection Applied to Metabolism and Cancer (GEBBAM), Federal University of Grande Dourados, Dourados, Brazil
- Tamaeh Monteiro-Alfredo
- Faculty of Medicine, Institute of Physiology, University of Coimbra, Coimbra, Portugal
- Tamaeh Monteiro-Alfredo
- Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, Portugal
- Tamaeh Monteiro-Alfredo
- Clinical Academic Center of Coimbra (CACC), University of Coimbra, Coimbra, Portugal
- Jéssica Maurino dos Santos
- Research Group on Biotechnology and Bioprospection Applied to Metabolism and Cancer (GEBBAM), Federal University of Grande Dourados, Dourados, Brazil
- Kátia Ávila Antunes
- Research Group on Biotechnology and Bioprospection Applied to Metabolism and Cancer (GEBBAM), Federal University of Grande Dourados, Dourados, Brazil
- Janielle Cunha
- Research Group on Biotechnology and Bioprospection Applied to Metabolism and Cancer (GEBBAM), Federal University of Grande Dourados, Dourados, Brazil
- Debora da Silva Baldivia
- Research Group on Biotechnology and Bioprospection Applied to Metabolism and Cancer (GEBBAM), Federal University of Grande Dourados, Dourados, Brazil
- Ana Salomé Pires
- Clinical Academic Center of Coimbra (CACC), University of Coimbra, Coimbra, Portugal
- Ana Salomé Pires
- Center for Innovative Biomedicine and Biotechnology (CIBB), University Coimbra, Coimbra, Portugal
- Ana Salomé Pires
- Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, University Coimbra, Coimbra, Portugal
- Inês Marques
- Clinical Academic Center of Coimbra (CACC), University of Coimbra, Coimbra, Portugal
- Inês Marques
- Center for Innovative Biomedicine and Biotechnology (CIBB), University Coimbra, Coimbra, Portugal
- Inês Marques
- Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, University Coimbra, Coimbra, Portugal
- Ana Margarida Abrantes
- Clinical Academic Center of Coimbra (CACC), University of Coimbra, Coimbra, Portugal
- Ana Margarida Abrantes
- Center for Innovative Biomedicine and Biotechnology (CIBB), University Coimbra, Coimbra, Portugal
- Ana Margarida Abrantes
- Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, University Coimbra, Coimbra, Portugal
- Maria Filomena Botelho
- Clinical Academic Center of Coimbra (CACC), University of Coimbra, Coimbra, Portugal
- Maria Filomena Botelho
- Center for Innovative Biomedicine and Biotechnology (CIBB), University Coimbra, Coimbra, Portugal
- Maria Filomena Botelho
- Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, University Coimbra, Coimbra, Portugal
- Lúcia Monteiro
- Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, University Coimbra, Coimbra, Portugal
- Ana Cristina Gonçalves
- Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, Portugal
- Ana Cristina Gonçalves
- Clinical Academic Center of Coimbra (CACC), University of Coimbra, Coimbra, Portugal
- Ana Cristina Gonçalves
- Center for Innovative Biomedicine and Biotechnology (CIBB), University Coimbra, Coimbra, Portugal
- Wellington Henrique Botelho
- Research Group on Biotechnology and Bioprospection Applied to Metabolism and Cancer (GEBBAM), Federal University of Grande Dourados, Dourados, Brazil
- Ana Paula de Araújo Boleti
- Research Group on Biotechnology and Bioprospection Applied to Metabolism and Cancer (GEBBAM), Federal University of Grande Dourados, Dourados, Brazil
- Célia Cabral
- Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, Portugal
- Célia Cabral
- Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
- Paulo J. Oliveira
- CNC—Center for Neuroscience and Cell Biology, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
- Edson Lucas dos Santos
- Research Group on Biotechnology and Bioprospection Applied to Metabolism and Cancer (GEBBAM), Federal University of Grande Dourados, Dourados, Brazil
- Paulo Matafome
- Faculty of Medicine, Institute of Physiology, University of Coimbra, Coimbra, Portugal
- Paulo Matafome
- Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, Portugal
- Paulo Matafome
- Clinical Academic Center of Coimbra (CACC), University of Coimbra, Coimbra, Portugal
- Paulo Matafome
- Department of Complementary Sciences, Instituto Politécnico de Coimbra, Coimbra Health School (ESTeSC), Coimbra, Portugal
- Kely de Picoli Souza
- Research Group on Biotechnology and Bioprospection Applied to Metabolism and Cancer (GEBBAM), Federal University of Grande Dourados, Dourados, Brazil
- DOI
- https://doi.org/10.3389/fphar.2023.1223933
- Journal volume & issue
-
Vol. 14
Abstract
Doxorubicin (Dox) is a chemotherapeutic agent widely used in the clinic, whose side effects include cardiotoxicity, associated with decreased antioxidant defenses and increased oxidative stress. The association of Dox with natural antioxidants can extend its use if not interfering with its pharmacological potential. In this study, we aimed to understand the effects and mechanisms of the aqueous extract of Acrocomia aculeata leaves (EA-Aa) in cancer cells and the co-treatment with Dox, in in vitro and in vivo models. It was found that EA-Aa showed a relevant decrease in the viability of cancer cells (K562 and MCF-7) and increased apoptosis and death. The Dox cytotoxic effect in co-treatment with EA-Aa was increased in cancer cells. The therapeutic association also promoted a change in cell death, leading to a higher rate of apoptosis compared to the Dox group, which induced necrosis. In addition, in non-cancer cells, EA-Aa enhanced red blood cell (RBC) redox state with lower hemolysis and malondialdehyde (MDA) content and had no in vitro nor in vivo toxicity. Furthermore, EA-Aa showed antioxidant protection against Dox-induced cytotoxicity in H9c2 cells (cardiomyoblast), partially mediated by the NRF2 pathway. In vivo, EA-Aa treatment showed a relevant decrease in MDA levels in the heart, kidney, and brain, evaluated in C57Bl/6 mice induced to cardiotoxicity by Dox. Together, our results proved the effectiveness of EA-Aa in potentiating Dox anticancer effects, with antioxidant and cardioprotective activity, suggesting EA-Aa as a potential Dox pharmacological adjuvant.
Keywords
