Efeitos antitumorais de chalconas sintéticas isoladas ou combinadas com temozolomida no tratamento de células de glioblastoma multiforme humano

Abstract

O glioblastoma (GBM) e o tumor cerebral mais comum e agressivo, com baixa taxa de sobrevida devido a sua alta proliferaça o, invasa o e resiste ncia a apoptose. O tratamento padra o envolve cirurgia, radioterapia e quimioterapia com temozolomida (TMZ), pore m, a resiste ncia ao tratamento limita a sua efica cia. Assim, e essencial desenvolver novas estrate gias terape uticas mais eficazes e menos agressivas, incluindo compostos que possam complementar tratamentos existentes, para aumentar a sobrevida e melhorar a qualidade de vida dos pacientes. Para isso, as chalconas se mostram promissoras devido aos seus diversos efeitos biolo gicos. Neste trabalho, foi analisado o efeito citoto xico de diversas chalconas em ce lulas de GBM, onde a chalcona Q1VA mostrou significativa reduça o de viabilidade celular e interfere ncia no ciclo celular, aumentando a apoptose e espe cies reativas de oxige nio em concentraço es especí ficas (capí tulo 1). O segundo capí tulo explorou o cotratamento de Q1VA e TMZ, o qual diminuiu a viabilidade celular e a adesa o a matriz extracelular, ale m de reduzir a produça o de EROs e a migraça o celular. Por fim, o terceiro capí tulo e composto de uma revisa o litera ria sobre a relaça o entre produtos naturais, como as chalconas na SUMOilaça o em gliomas. Juntos, nossos resultados demonstram que as chalconas podem reduzir a proliferaça o e invasa o celular, aumentando a apoptose, sugerindo que essas mole culas poderiam influenciar vias de sinalizaça o importantes. Mais especificamente, a chalcona Q1VA demonstrou potenciais resultados contra ce lulas de GBM. Desta forma, esses efeitos observados devem ser estudados de forma mais detalhada.

Abstract: Glioblastoma (GBM) is the most common and aggressive brain tumor, with a low survival rate due to its high proliferation, invasion and resistance to apoptosis. Standard treatment involves surgery, radiotherapy and chemotherapy with temozolomide (TMZ), however, resistance to treatment limits its effectiveness. Therefore, it is essential to develop new, more effective and less aggressive therapeutic strategies, including compounds that can complement existing treatments, to increase survival and improve patients' quality of life. To this end, chalcones show promise due to their diverse biological effects. In this work, the cytotoxic effect of several chalcones on GBM cells was analyzed, where the chalcone Q1VA showed a significant reduction in cell viability and interference in the cell cycle, increasing apoptosis and ROS in specific concentrations (chapter 1). The second chapter explored the co-treatment of Q1VA and TMZ, which decreased cell viability and adhesion to the extracellular matrix, in addition to reducing ROS production and cell migration. Finally, the third chapter consists of a literary review on the relationship between natural products, such as chalcones, in SUMOylation in gliomas. Together, our results demonstrate that chalcones can reduce cell proliferation and invasion, increasing apoptosis, suggesting that these molecules could influence important signaling pathways. More specifically, chalcone Q1VA demonstrated potential results against GBM cells. Therefore, these observed effects should be studied in more detail.