Role of a Novel Heparanase Inhibitor on the Balance between Apoptosis and Autophagy in U87 Human Glioblastoma Cells

Autor: Valeria Manganelli, Roberta Misasi, Gloria Riitano, Antonella Capozzi, Vincenzo Mattei, Tuba Rana Caglar, Davide Ialongo, Valentina Noemi Madia, Antonella Messore, Roberta Costi, Roberto Di Santo, Maurizio Sorice, Tina Garofalo
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cells, Vol 12, Iss 14, p 1891 (2023)
Druh dokumentu: article
ISSN: 2073-4409
DOI: 10.3390/cells12141891
Popis: Background: Heparanase (HPSE) is an endo-β-glucuronidase that cleaves heparan sulfate side chains, leading to the disassembly of the extracellular matrix, facilitating cell invasion and metastasis dissemination. In this research, we investigated the role of a new HPSE inhibitor, RDS 3337, in the regulation of the autophagic process and the balance between apoptosis and autophagy in U87 glioblastoma cells. Methods: After treatment with RDS 3337, cell lysates were analyzed for autophagy and apoptosis-related proteins by Western blot. Results: We observed, firstly, that LC3II expression increased in U87 cells incubated with RDS 3337, together with a significant increase of p62/SQSTM1 levels, indicating that RDS 3337 could act through the inhibition of autophagic-lysosomal flux of LC3-II, thereby leading to accumulation of lipidated LC3-II form. Conversely, the suppression of autophagic flux could activate apoptosis mechanisms, as revealed by the activation of caspase 3, the increased level of cleaved Parp1, and DNA fragmentation. Conclusions: These findings support the notion that HPSE promotes autophagy, providing evidence that RDS 3337 blocks autophagic flux. It indicates a role for HPSE inhibitors in the balance between apoptosis and autophagy in U87 human glioblastoma cells, suggesting a potential role for this new class of compounds in the control of tumor growth progression.
Databáze: Directory of Open Access Journals
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