Bibliographic Details
| Title: |
Role of a Novel Heparanase Inhibitor on the Balance between Apoptosis and Autophagy in U87 Human Glioblastoma Cells |
| Authors: |
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 |
| Source: |
Cells, Vol 12, Iss 14, p 1891 (2023) |
| Publisher Information: |
MDPI AG, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
heparanase inhibitor, apoptosis, autophagy, U87 human glioblastoma cells, Cytology, QH573-671 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2073-4409 |
| Relation: |
https://www.mdpi.com/2073-4409/12/14/1891; https://doaj.org/toc/2073-4409 |
| DOI: |
10.3390/cells12141891 |
| Access URL: |
https://doaj.org/article/4a6d6815a3b94fd9b93af0311f16cea2 |
| Accession Number: |
edsdoj.4a6d6815a3b94fd9b93af0311f16cea2 |
| Database: |
Directory of Open Access Journals |
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