Efeitos dos extratos de Euterpe oleracea e Geissospermum vellosii em linhagens celulares de câncer cervical

Abstract

Cervical cancer is an important public health problem, being the fourth cause of death in women in Brazil and the third most common tumor in the state of Maranhão, with therapeutic options of limited effectiveness and with significant side effects. Euterpe oleracea and Geissospermum vellosii are plant species found in the Maranhão Amazon, rich, respectively, in polyphenols and indole alkaloids, classes of compounds with recognized antineoplastic activities. The açaí seed corresponds to most of the fruit and represents a waste product, with a significant environmental impact. In addition, previous studies show an antitumor effect of the components of the seed, superior to the other parts of the fruit. This work aimed to evaluate the antitumor effects of E. oleracea seed and G. vellosii stem bark extracts on cervical cancer cell lines. The hydroalcoholic extract of the seed of E. oleracea was prepared from the fruits collected in the municipalities of Axixá, Morros, São Luís and Presidente Juscelino. After removing the pulp, crushing the seeds and hydroalcoholic percolation, rotavaporation and lyophilization were performed. Chemical characterization was performed by high performance liquid chromatography, followed by mass spectrometry. The ethanolic extract of the stem bark of G. vellosii previously prepared and chemically characterized was also tested. The extracts were tested on cervical cancer cell lines (HeLa and SiHa) and normal human lung fibroblast (GM) in order to observe changes in cell viability and morphology and compare them to the effects caused by gemcitabine. Through chemical characterization, it was found that E. oleracea seed extract contains catechins and procyanidins as its predominant components. This extract showed a reduction in cell viability of SiHa and HeLa at a concentration of 120μg/ml, in addition to inducing discrete morphological changes. The G. vellosii extract showed great potential to reduce cell viability in a time and concentration dependent manner in all cell lines, with IC50 of 25.46 ± 2.18 and 53.08 ± 2.45 μg/mL for HeLa and SiHa, respectively. The morphology of these cells was significantly affected by the presence of the extract, with a reduction in cell area. The stem bark extract of G. vellosii showed more promising antineoplastic potential, with greater cytotoxicity and greater sensitivity of the tumor lineage related to HPV-18 (HeLa) at low concentrations, when compared to the normal cell line. Furthermore, it was able to significantly reduce the formation of tumor cell colonies after treatment. There was also a favorable antitumor effect in the association of extracts of E. oleracea and G. vellosii among themselves and with gemcitabine, with increased cytotoxicity in tumor cells, without significantly reducing the viability of normal cells tested. One of the main innovations of this work is the potential of extracts as adjuvants in antineoplastic treatment.