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Estudo do papel do ácido betulínico na diferenciação adipocítica e na angiogénese tumoral
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O glioblastoma é o tumor maligno mais comum do sistema nervoso central, caracterizando-se por elevada incidência e baixa taxa de sobrevivência A angiogénese é crucial para a progressão tumoral, enquanto a obesidade surge como um fator de risco, associada a inflamação crónica, que modula, por sua vez, processos como a angiogénese, proliferação celular e a resistência terapêutica. O ácido betulínico (BA) com propriedades anticancerígenas e anti-adipogénicas, é um candidato promissor no contexto do glioblastoma e da obesidade. O objetivo deste estudo foi investigar os efeitos do BA nos processos de viabilidade celular, diferenciação de pré-adipócitos e na angiogénese, utilizando modelos in vitro. Assim, avaliou-se o efeito do BA na viabilidade celular da linha celular tumoral U251 e numa linha normal. O efeito do composto na diferenciação adipocítica nas 3T3-L1 foi analisado por microscopia ótica e quantificação após coloração Oil Red O e a angiogénese foi avaliada através do ensaio de formação de tubos em Matrigel. Os resultados demonstram que o BA reduz significativamente a viabilidade das células U251 de forma dependente da dose, sem afetar a viabilidade das células normais. Observou-se uma diminuição significativa da acumulação de gotículas lipídicas, sugerindo um efeito inibitório na diferenciação adipogénica. Por sua vez, o ensaio de angiogénese, verificou uma redução da formação de redes tubulares em todas as concentrações testadas, sendo o efeito mais marcado a 1 μM. Em suma, os resultados deste estudo sugerem que o BA possui um perfil promissor como agente terapêutico no glioblastoma, combinando efeitos anti-adipogénicos, anti-angiogénicos e seletividade citotóxica para células tumorais.
Glioblastoma is the most common malignant tumor of the central nervous system, characterized by high incidence and poor survival. Angiogenesis plays a crucial role in tumor progression, while obesity has emerged as a risk factor associated with chronic inflammation, which in turn modulates processes such as angiogenesis, cell proliferation, and therapy resistance. Betulinic acid (BA), a natural triterpenoid with anticancer and anti-adipogenic properties, is a promising candidate for glioblastoma and obesity. This study aimed to investigate the effects of BA on viability, preadipocyte differentiation and angiogenesis, using in vitro models. Accordingly, the effect of BA on the viability of the U251 tumor cell line and a normal cell line was evaluated. The compound’s effect on adipocyte differentiation in 3T3-L1 cells was evaluated by microscopy and quantified after Oil Red O staining, while angiogenesis was assessed through a Matrigel tube formation assay. The results show that BA significantly reduced the viability of U251 cells in a dose-dependent manner, without affecting the viability of normal cells. A significant decrease in the accumulation of lipid droplets was observed, suggesting an inhibitory effect on adipogenic differentiation. In the angiogenesis assay, the formation of endothelial tubes was reduced at all tested concentrations with the most pronounced effect observed at 1 μM. In conclusion, the results of this study suggest that BA has a promising profile as a therapeutic agent in glioblastoma, combining anti-adipogenic and anti-angiogenic effects with selective cytotoxicity toward cancer cells.
Glioblastoma is the most common malignant tumor of the central nervous system, characterized by high incidence and poor survival. Angiogenesis plays a crucial role in tumor progression, while obesity has emerged as a risk factor associated with chronic inflammation, which in turn modulates processes such as angiogenesis, cell proliferation, and therapy resistance. Betulinic acid (BA), a natural triterpenoid with anticancer and anti-adipogenic properties, is a promising candidate for glioblastoma and obesity. This study aimed to investigate the effects of BA on viability, preadipocyte differentiation and angiogenesis, using in vitro models. Accordingly, the effect of BA on the viability of the U251 tumor cell line and a normal cell line was evaluated. The compound’s effect on adipocyte differentiation in 3T3-L1 cells was evaluated by microscopy and quantified after Oil Red O staining, while angiogenesis was assessed through a Matrigel tube formation assay. The results show that BA significantly reduced the viability of U251 cells in a dose-dependent manner, without affecting the viability of normal cells. A significant decrease in the accumulation of lipid droplets was observed, suggesting an inhibitory effect on adipogenic differentiation. In the angiogenesis assay, the formation of endothelial tubes was reduced at all tested concentrations with the most pronounced effect observed at 1 μM. In conclusion, the results of this study suggest that BA has a promising profile as a therapeutic agent in glioblastoma, combining anti-adipogenic and anti-angiogenic effects with selective cytotoxicity toward cancer cells.
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Saúde Glioblastoma Obesidade Ácido betulínico Diferenciação Angiogénese