Evaluación del efecto antitumoral de 4-Metilumbeliferona y estudio de blancos moleculares relacionados con el metabolismo del ácido hialurónico en líneas celulares de glioblastoma
Glioblastoma (GBM) is the most frequent and aggressive tumor of the central nervous system (CNS). Hyaluronan (HA), the major component in the brain cellular matrix, has been correlated with GBM progression. 4-methylumbelliferone (4MU), an inhibitor of HA synthesis, showed anti-tumor effects on sever...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
2020
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_6350 https://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_6350.dir/6350.PDF |
| Aporte de: |
| Sumario: | Glioblastoma (GBM) is the most frequent and aggressive tumor of the central nervous system (CNS). Hyaluronan (HA), the major component in the brain cellular matrix, has been correlated with GBM progression. 4-methylumbelliferone (4MU), an inhibitor of HA synthesis, showed anti-tumor effects on several models, without evidence of adverse effects. However, 4MU has not been studied in GBM.\nHypothesis: 4MU alone or in combination with temozolomide could be a future therapeutic alternative for GBM.\nGeneral Aim: To evaluate the effect of 4MU, HA, temozolomide and their combinations on several processes on GBM cells, the toxicity of 4MU on normal cells of CNS and the modulation of CD44, RHAMM as well as the MEK/ERK pathway, and their implication in the migration of GBM cells.\n4MU generated a great and selective anti-tumoral effect. The combination 4MU + Temozolomide improved the effects compared to each drug alone. Furthermore, the majority of the effects of 4MU would seem to be independent of the inhibition of HA synthesis. HA augmented the migration and CD44, RHAMM and MEK were involved in such process and were modulated by 4MU.\nIn conclusion, 4MU is postulated, alone or in combination with temozolomide, as a future therapeutic alternative for GBM. |
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