POTENCIAL EFEITO ANTICARCINOGÊNICO E NA ATIVIDADE QUIMIOTERÁPICA IN VITRO DO EXTRATO DE CACAU (Theobroma cacao L.) EM CÉLULAS DE LEUCEMIA MIELOCÍTICA CRÔNICA (K562)

• Autor(a) principal: Lopes, Aline Costa
• Data de Publicação: 2021
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional Universidade Franciscana
• Texto Completo: http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/1048
• topic: Cacau, Câncer, Resistência Tumoral, Ácido trans-retinóico, Efeito Anticarcinogênico.; Cocoa, Cancer, Tumor Resistance, All-trans Retinoic Acid, Anticarcinogenic effect.; Ciências da Saúde e da Vida

Chronic myeloid leukemia (CML) is a myeloproliferative disorder altered by neoplastic transformation of the hematopoietic stem cell and the pathognomonic presence of the Philadelphia chromosome (Ph), resulting from a reciprocal translocation between chromosomes 9 and 22. The best therapeutic treatment used for CLM involves the target-molecular chemotherapy with all-trans-retinoic acid (ATRA) and arsenic trioxide. However, beyond some patients being resistant to the treatments, some drugs can also cause damage to healthy cells, that have frequent growth, which contributes to side effects. Therefore, new therapeutic alternatives must be revealed. Thus, studies are looking for new antitumor agents that can help against these possible side effects and drug resistance, to obtain the best results, mainly through natural compounds. In this context, cocoa (Theobroma cacao L.) is included, a fruit used for centuries in the production of chocolate. Moreover, this functional food is also being widely explored for its medicinal action, since it has several bioactive molecules in its chemical matrix, which guarantee important biological properties, such as antiinflammatory, antioxidant, and antitumor. In this scenario, the aim of this study was to investigate whether cocoa extract (Theobroma cacao L.) would have an in vitro anticarcinogenic effect and in chemotherapeutic activity in CML cells (K562). For this, K562 cells were exposed to different concentrations of aqueous cocoa extract (30; 100; 500; 750; 1000; 1500 and 2000 μg/mL) during 24 and 72 hours of incubation. In addition, the effect of cocoa extract was analyzed associated with chemotherapeutics ATRA (1 μM) and arsenic trioxide (250 μg/mL). After the incubation periods, assays were performed to measure the levels of cell viability and proliferation as well as oxidative stress. In addition, the fibroblast line (HFF-1) was exposed to the same concentrations of cocoa extract used for the treatment of K562, in order to identify a possible cytotoxic effect. The results found in this study revealed that the cocoa extract was able to decrease the viability levels of K562 cells exposed to the highest concentrations (1000, 1500 and 2000 μg/mL) during 24 hours of incubation, although for 72 hours of exposure the extract cocoa reduced the levels of cell proliferation in all tested concentration. The anticarcinogenic mechanism of cocoa can be explained by the production of oxidative stress, generated by the increase in the levels of total ROS, nitric oxide and superoxide. In addition, cocoa increased the action of chemotherapy, by reducing cell viability and proliferation. Additionally, cocoa had a selective cytotoxic effect, since the extract did not cause damage to fibroblasts in any tested concentration. Therefore, cocoa has a cytotoxic effect on K562 cells and improves the chemotherapeutic action, without affecting normal cells, highlighting cocoa as a potent anticarcinogenic agent, which has a great potential to be used for therapies with no side effects for CML.