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Betulinic acid modulates adipocyte differentiation and secretome activity: Downstream effects on Glioblastoma cell migration

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Resumo(s)

Betulinic acid (BA) has been recognized for its po-tential to modulate tumor progression and adipocyte function, yet its effects on adipocyte secretome re-modeling and the downstream consequences for glio-blastoma behavior remain incompletely understood1-4. In this study, we investigated the influence of BA on adipocyte secretory activity and its functional impact on glioblastoma cell migration. Direct exposure of U251 glioblastoma cells to BA significantly reduced cell migration, confirming its intrinsic anti-migratory potential. To further explore microenvironmental in-teractions, adipocyte-conditioned media (ACM) de-rived from BA-treated adipocytes was evaluated for its effects on glioblastoma behavior. Secretome anal-ysis demonstrated that BA altered matrix metallopro-teinase (MMP) expression and reduced gelatinolytic activity, indicating significant modulation of extracel-lular matrix–related proteolytic pathways. Functional assessment using wound healing assays revealed that ACM from BA-treated adipocytes did not consistent-ly suppress glioblastoma migration. Intermediate BA concentrations were associated with increased migratory behavior relative to basal conditions, although differences compared with control ACM were not statistically significant. Additionally, transwell migra-tion assays did not demonstrate significant differ-ences between treatment conditions, suggesting that BA-induced alterations in adipocyte secretome com-position do not uniformly translate into measurable changes in glioblastoma migratory capacity across dif-ferent experimental models. These findings indicate that modulation of gelatinolytic pathways alone is insufficient to predict glioblastoma cell migration and support the contribution of additional adipocyte-de-rived signalling mechanisms in regulating tumor be-havior. Overall, BA induces substantial remodelling of adipocyte secretory function, producing complex and non-linear downstream effects on glioblastoma cells. This study highlights the importance of tumor micro-environment crosstalk and underscores the need to evaluate multiple regulatory pathways when consid-ering the therapeutic potential of BA and related bio-active compounds.

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Betulinic acid Obesity Glioblastoma multiforme

Contexto Educativo

Citação

Gouveia, A., Ferraz, R., Prudêncio, C., & Fernandes, S. (2026). Betulinic acid modulates adipocyte differentiation and secretome activity: Downstream effects on Glioblastoma cell migration. Book of Abstracts of the 8th Meeting on Medicinal Biotechnology, 35. https://edicoes.ipp.pt/index.php/books/catalog/book/251

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