Revisão de tratamentos anticâncer e atividade antitumoral de extratos pirolenhosos sobre glioblastoma humano (GBM02)

Abstract

Bioactive compounds from plants play a fundamental role in antitumor therapy, providing new alternatives for the development of future drugs. Therefore, a review was prepared that addresses the anticancer effects of bioactive compounds present in the plant Cocos nucifera, which has anti-inflammatory, antimicrobial, antioxidant, anthelmintic and anticancer activities. Searches were carried out in several databases between January and February 2024 using the keywords cocos nucifera AND cancer. A total of 554 articles were found and 32 studies included following the inclusion and exclusion criteria. The annual distribution of publications, the type of test performed (25 in vitro, 3 in vivo, 1 in silico and 3 had more than one test), the country of publication, the portions of the coconut tree used and the type of cancer evaluated were performed. The review highlights the potential anticancer activity and the importance of research with C. nucifera and its bioactive compounds that can disrupt the mechanisms of maturation, differentiation and proliferation of cancer cells. We found that clinical studies with C. nucifera are absent in the literature. In the second stage, in vitro studies were performed with Glioblastoma (GBM) cells. GBM is the primary malignant glial tumor of the Central Nervous System (CNS) associated with high rates of morbidity and mortality due to its high degree of proliferation and invasiveness, where patient survival is around 15 months. Therefore, the search for alternative drugs for the treatment of GBM is urgent. In this sense, pyrolysis is a technique for obtaining extracts through the thermochemical process of transforming biomass into pyroligneous extract, which has wide fungicidal, herbicidal and insecticidal application, and in this study its antitumor effects were evaluated. Initially, the MTT colorimetric assay was performed to evaluate the effects of the extracts on the viability of GBM02 and blood mononuclear cells (monocytes and lymphocytes). Then, the selectivity of the extracts was calculated using the ratio between monocytes and lymphocytes (CC50) and GBM02 (IC50). Finally, the antimigratory effects were evaluated and morphological analyses of GBM02 were performed using optical microscopy. None of the tested extracts were toxic (CC50>1) to monocytes and lymphocytes. Among the extracts that inhibited GBM02 viability, the most effective were EP-EUCL (57.19 ± 2.66%), EP-DABR (56.93 ± 2.77%), EP-PPCE (55.44 ± 2.57%), EP-CPCK (51.08 ± 3.11%) and, among them, the most potent was EP-EUCL (0.132% ± 0.007). The EP-EUCL (IS >7.5, EP-CPCK (IS >5.7), EP-DABR (IS >5.5) (EP PPCE >5.3) extracts were more selective for GBM02 than for monocytes and lymphocytes. Among these, EP-EUCL and EP-PPCE inhibited GBM02 migration by 99.24%** and 93.51%*, respectively. The protoplasmic morphology, characteristic of GBM, was observed in cells treated with DMEM-F12, and in treatments with EPs, there was the appearance of cells with rounded cytoplasm, formation of cytoplasmic vacuoles and rupture of cell and nuclear membranes, typical of cell death. Among all the extracts, EP-EUCL and EP-PPCE were the ones that presented the most satisfactory antitumor activity. Thus, these extracts proved to be promising agents for drug development, with the purpose of becoming a future therapeutic option for GBM.