多柔比星（Dox）是一种广泛应用于临床的化疗药物，其副作用包括心脏毒性，与抗氧化防御力下降和氧化应激增加有关。多柔比星与天然抗氧化剂的联合应用可以扩展其使用范围，而不会干扰其药理潜力。本研究旨在了解Acrocomia aculeata叶提取物（EA-Aa）对癌细胞及其与多柔比星联合治疗的影响和机制，使用体外和体内模型进行研究。结果显示，EA-Aa显著降低了癌细胞（K562和MCF-7）的存活率，并增加了细胞凋亡和死亡。在与EA-Aa联合治疗时，多柔比星对癌细胞的细胞毒作用增强。治疗联合还促使细胞死亡方式发生变化，导致更高比例的凋亡，而多柔比星诱导了坏死。此外，EA-Aa在非癌细胞中增强了红细胞（RBC）的氧化还原状态，减少了溶血和丙二醛（MDA）含量，并且没有体外和体内毒性。此外，EA-Aa在H9c2细胞（心肌母细胞）中对多柔比星诱导的细胞毒性具有一定的抗氧化保护作用，部分通过NRF2途径介导。在体内，EA-Aa治疗显著降低了Dox诱导的C57Bl/6小鼠心脏、肾脏和大脑的MDA水平。综上所述，我们的结果证明了EA-Aa增强多柔比星的抗癌效果，并具有抗氧化和心脏保护活性，提示EA-Aa作为潜在的多柔比星辅助药物。版权所有©2023 Monteiro-Alfredo, dos Santos, Antunes, Cunha, da Silva Baldivia, Pires, Marques, Abrantes, Botelho, Monteiro, Gonçalves, Botelho, Paula de Araújo Boleti, Cabral, Oliveira, Lucas dos Santos, Matafome和de Picoli Souza.

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.Copyright © 2023 Monteiro-Alfredo, dos Santos, Antunes, Cunha, da Silva Baldivia, Pires, Marques, Abrantes, Botelho, Monteiro, Gonçalves, Botelho, Paula de Araújo Boleti, Cabral, Oliveira, Lucas dos Santos, Matafome and de Picoli Souza.