Betulinic Acid properties in the invasive profile of glioblastoma

Sousa, António José Silva Ferreira de

http://hdl.handle.net/10400.22/29550

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Authors

Sousa, António José Silva Ferreira de

Advisor(s)

Fernandes, Sílvia

Ferraz, Ricardo

Abstract(s)

Glioblastoma is the most frequent and most malignant primary brain neoplasia. The standard therapy, based on surgical resection, followed by radiation therapy and temozolomide, has not been effective. The complex system of signaling pathways and interactions with the extracellular matrix and host cells is at the root of the invasive phenotype of glioblastoma. For this reason, unveiling novel compounds and new therapeutic approaches against this cancer is of utmost importance. Betulinic acid has previously demonstrated selective antitumor activity in several cancer cell types as well as beneficial effects on neurological disorders, showing great potential to be used for glioblastoma treatment strategies. The main objective of this work is to evaluate the effects of betulinic acid on the invasive profile of glioblastoma. Thus, A172 and U251 glioblastoma cell lines were treated with previously selected doses of betulinic acid and the effect on invasion and migration of the cells was evaluated through the transwell invasion assay and wound healing assay. Moreover, mRNA levels of different keyplayers were quantified using qPCR methodology. The results showed that betulinic acid can counteract the migration pattern of glioblastoma cell lines, in all timepoints studied, particularly for the 2.5 μM dose. Alterations found on mRNA levels of some genes assessed in the present study seem to show that EGFR-STAT3 pathway blockade could be involved in the molecular action of BA. These are important findings regarding the molecular mechanisms involved in BA action, although further studies are needed. The anti-invasive effects of betulinic acid, together with its ability to cross the blood-brain barrier and other anti-tumor properties, is a promising sign that this compound could constitute a novel therapeutic approach with better clinical outcomes.