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In Vitro and Computational Studies of Perezone and Perezone Angelate as Potential Anti-Glioblastoma Multiforme Agents.

ABSTRACT: Glioblastoma multiforme (GBM) represents the most malignant type of astrocytoma, with a life expectancy of two years. It has been shown that Poly (ADP-ribose) polymerase 1 (PARP-1) protein is over-expressed in GBM cells, while its expression in healthy tissue is low. In addition, perezone, a phyto-compound, is a PARP-1 inhibitor with anti-neoplastic activity. As a consequence, in the present study, both in vitro and computational evaluations of perezone and its chemically related compound, perezone angelate, as anti-GBM agents were performed. Hence, the anti-proliferative assay showed that perezone angelate induces higher cytotoxicity in the GBM cell line (U373 IC50 = 6.44 μM) than perezone (U373 IC50 = 51.20 μM) by induction of apoptosis. In addition, perezone angelate showed low cytotoxic activity in rat glial cells (IC50 = 173.66 μM). PARP-1 inhibitory activity (IC50 = 5.25 μM) and oxidative stress induction by perezone angelate were corroborated employing in vitro studies. In the other hand, the performed docking studies allowed explaining the PARP-1 inhibitory activity of perezone angelate, and ADMET studies showed its probability to permeate cell membranes and the blood-brain barrier, which is an essential characteristic of drugs to treat neurological diseases. Finally, it is essential to highlight that the results confirm perezone angelate as a potential anti-GBM agent.

SUBMITTER: Hernandez-Rodriguez M

PROVIDER: S-EPMC8911992 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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In Vitro and Computational Studies of Perezone and Perezone Angelate as Potential Anti-Glioblastoma Multiforme Agents.

Hernández-Rodríguez Maricarmen M Mendoza Sánchez Pablo I PI Martínez Joel J Macías Pérez Martha E ME Rosales Cruz Erika E Żołek Teresa T Maciejewska Dorota D Miranda Ruvalcaba René R Mera Jiménez Elvia E Nicolás-Vázquez María I MI

Molecules (Basel, Switzerland) 20220226 5

Glioblastoma multiforme (GBM) represents the most malignant type of astrocytoma, with a life expectancy of two years. It has been shown that Poly (ADP-ribose) polymerase 1 (PARP-1) protein is over-expressed in GBM cells, while its expression in healthy tissue is low. In addition, perezone, a phyto-compound, is a PARP-1 inhibitor with anti-neoplastic activity. As a consequence, in the present study, both in vitro and computational evaluations of perezone and its chemically related compound, perez ...[more]

PMID: 35268667

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Project description:MicroRNAs (miRNAs or miRs) contribute to the development of various malignant neoplasms, including glioblastoma multiforme (GBM). The present study aimed to explore the pathogenesis of GBM and to identify latent therapeutic agents for patients with GBM, based on an in silico analysis. Gene chips that provide miRNA expression profiling in GBM were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEMs) were also determined via the RobustRankAggreg algorithm. The target genes of DEMs were predicted and then intersected with GBM‑associated genes that were collected from the Gene Expression Profiling Interactive Analysis. Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the overlapping genes were then performed. Simultaneously, a connectivity map (CMap) analysis was performed to screen for potential therapeutic agents for GBM. A total of 10 DEMs (hsa‑miR‑196a, hsa‑miR‑10b, hsa‑miR‑196b, hsa‑miR‑18b, hsa‑miR‑542‑3p, hsa‑miR‑129‑3p, hsa‑miR‑1224‑5p, hsa‑miR‑876‑3p and hsa‑miR‑770‑5p) were obtained from three GEO gene chips (GSE25631, GSE42657 and GSE61710). Then, 1,720 target genes of the 10 miRNAs and 4,185 differently expressed genes in GBM were collected. By intersecting the aforementioned gene clusters, the present study identified 390 overlapping genes. GO and KEGG analyses of the 390 genes demonstrated that these genes were involved in certain cancer‑associated biological functions and pathways. Eight genes [(GTPase NRas (NRAS), calcium/calmodulin‑dependent protein kinase type II subunit Gamma (CAMK2G), platelet‑derived growth factor receptor alpha (PDGFRA), calmodulin 3 (CALM3), cyclin‑dependent kinase 6 (CDK6), calcium/calmodulin‑dependent protein kinase type II subunit beta (CAMK2B), retinoblastoma‑associated protein (RB1) and protein kinase C beta type (PRKCB)] that were centralized in the glioma pathway were selected for CMap analysis. Three chemicals (W‑13, gefitinib and exemestane) were identified as putative therapeutic agents for GBM. In summary, the present study identified three miRNA‑based chemicals for use as a therapy for GBM. However, more experimental data are needed to verify the therapeutic properties of these latent drugs in GBM.

Dataset Information

In Vitro and Computational Studies of Perezone and Perezone Angelate as Potential Anti-Glioblastoma Multiforme Agents.

Publications

In Vitro and Computational Studies of Perezone and Perezone Angelate as Potential Anti-Glioblastoma Multiforme Agents.

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