Cargando…
Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis
Glioblastoma multiforme (GBM) is a lethal malignant tumor accounting for 42% of the tumors of the central nervous system, the median survival being 15 months. At present, no curative treatment is available for GBM and new drugs and therapeutic protocols are urgently needed. In this context, combined...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875359/ https://www.ncbi.nlm.nih.gov/pubmed/35209084 http://dx.doi.org/10.3390/molecules27041299 |
_version_ | 1784657893903040512 |
---|---|
author | Gasparello, Jessica Papi, Chiara Zurlo, Matteo Gambari, Laura Rozzi, Andrea Manicardi, Alex Corradini, Roberto Gambari, Roberto Finotti, Alessia |
author_facet | Gasparello, Jessica Papi, Chiara Zurlo, Matteo Gambari, Laura Rozzi, Andrea Manicardi, Alex Corradini, Roberto Gambari, Roberto Finotti, Alessia |
author_sort | Gasparello, Jessica |
collection | PubMed |
description | Glioblastoma multiforme (GBM) is a lethal malignant tumor accounting for 42% of the tumors of the central nervous system, the median survival being 15 months. At present, no curative treatment is available for GBM and new drugs and therapeutic protocols are urgently needed. In this context, combined therapy appears to be a very interesting approach. The isothiocyanate sulforaphane (SFN) has been previously shown to induce apoptosis and inhibit the growth and invasion of GBM cells. On the other hand, the microRNA miR-15b is involved in invasiveness and proliferation in GBM and its inhibition is associated with the induction of apoptosis. On the basis of these observations, the objective of the present study was to determine whether a combined treatment using SFN and a peptide nucleic acid interfering with miR-15b-5p (PNA-a15b) might be proposed for increasing the pro-apoptotic effects of the single agents. To verify this hypothesis, we have treated GMB U251 cells with SFN alone, PNA-a15b alone or their combination. The cell viability, apoptosis and combination index were, respectively, analyzed by calcein staining, annexin-V and caspase-3/7 assays, and RT-qPCR for genes involved in apoptosis. The efficacy of the PNA-a15b determined the miR-15b-5p content analyzed by RT-qPCR. The results obtained indicate that SFN and PNA-a15b synergistically act in inducing the apoptosis of U251 cells. Therefore, the PNA-a15b might be proposed in a “combo-therapy” associated with SFN. Overall, this study suggests the feasibility of using combined treatments based on PNAs targeting miRNA involved in GBM and nutraceuticals able to stimulate apoptosis. |
format | Online Article Text |
id | pubmed-8875359 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88753592022-02-26 Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis Gasparello, Jessica Papi, Chiara Zurlo, Matteo Gambari, Laura Rozzi, Andrea Manicardi, Alex Corradini, Roberto Gambari, Roberto Finotti, Alessia Molecules Article Glioblastoma multiforme (GBM) is a lethal malignant tumor accounting for 42% of the tumors of the central nervous system, the median survival being 15 months. At present, no curative treatment is available for GBM and new drugs and therapeutic protocols are urgently needed. In this context, combined therapy appears to be a very interesting approach. The isothiocyanate sulforaphane (SFN) has been previously shown to induce apoptosis and inhibit the growth and invasion of GBM cells. On the other hand, the microRNA miR-15b is involved in invasiveness and proliferation in GBM and its inhibition is associated with the induction of apoptosis. On the basis of these observations, the objective of the present study was to determine whether a combined treatment using SFN and a peptide nucleic acid interfering with miR-15b-5p (PNA-a15b) might be proposed for increasing the pro-apoptotic effects of the single agents. To verify this hypothesis, we have treated GMB U251 cells with SFN alone, PNA-a15b alone or their combination. The cell viability, apoptosis and combination index were, respectively, analyzed by calcein staining, annexin-V and caspase-3/7 assays, and RT-qPCR for genes involved in apoptosis. The efficacy of the PNA-a15b determined the miR-15b-5p content analyzed by RT-qPCR. The results obtained indicate that SFN and PNA-a15b synergistically act in inducing the apoptosis of U251 cells. Therefore, the PNA-a15b might be proposed in a “combo-therapy” associated with SFN. Overall, this study suggests the feasibility of using combined treatments based on PNAs targeting miRNA involved in GBM and nutraceuticals able to stimulate apoptosis. MDPI 2022-02-15 /pmc/articles/PMC8875359/ /pubmed/35209084 http://dx.doi.org/10.3390/molecules27041299 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gasparello, Jessica Papi, Chiara Zurlo, Matteo Gambari, Laura Rozzi, Andrea Manicardi, Alex Corradini, Roberto Gambari, Roberto Finotti, Alessia Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis |
title | Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis |
title_full | Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis |
title_fullStr | Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis |
title_full_unstemmed | Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis |
title_short | Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis |
title_sort | treatment of human glioblastoma u251 cells with sulforaphane and a peptide nucleic acid (pna) targeting mir-15b-5p: synergistic effects on induction of apoptosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875359/ https://www.ncbi.nlm.nih.gov/pubmed/35209084 http://dx.doi.org/10.3390/molecules27041299 |
work_keys_str_mv | AT gasparellojessica treatmentofhumanglioblastomau251cellswithsulforaphaneandapeptidenucleicacidpnatargetingmir15b5psynergisticeffectsoninductionofapoptosis AT papichiara treatmentofhumanglioblastomau251cellswithsulforaphaneandapeptidenucleicacidpnatargetingmir15b5psynergisticeffectsoninductionofapoptosis AT zurlomatteo treatmentofhumanglioblastomau251cellswithsulforaphaneandapeptidenucleicacidpnatargetingmir15b5psynergisticeffectsoninductionofapoptosis AT gambarilaura treatmentofhumanglioblastomau251cellswithsulforaphaneandapeptidenucleicacidpnatargetingmir15b5psynergisticeffectsoninductionofapoptosis AT rozziandrea treatmentofhumanglioblastomau251cellswithsulforaphaneandapeptidenucleicacidpnatargetingmir15b5psynergisticeffectsoninductionofapoptosis AT manicardialex treatmentofhumanglioblastomau251cellswithsulforaphaneandapeptidenucleicacidpnatargetingmir15b5psynergisticeffectsoninductionofapoptosis AT corradiniroberto treatmentofhumanglioblastomau251cellswithsulforaphaneandapeptidenucleicacidpnatargetingmir15b5psynergisticeffectsoninductionofapoptosis AT gambariroberto treatmentofhumanglioblastomau251cellswithsulforaphaneandapeptidenucleicacidpnatargetingmir15b5psynergisticeffectsoninductionofapoptosis AT finottialessia treatmentofhumanglioblastomau251cellswithsulforaphaneandapeptidenucleicacidpnatargetingmir15b5psynergisticeffectsoninductionofapoptosis |