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Autophagy Inhibition via Hydroxychloroquine or 3-Methyladenine Enhances Chemotherapy-Induced Apoptosis in Neuro-Blastoma and Glioblastoma

Neuroblastoma is the most common tumour in children under 1 year old, accounting for 12–15% of childhood cancer deaths. Although current treatments are relatively efficacious against this cancer, associated adverse effects could be detrimental to growth and development. In contrast, glioblastoma acc...

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Autores principales: Wear, Darcy, Bhagirath, Eesha, Balachandar, Arpana, Vegh, Caleb, Pandey, Siyaram
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418453/
https://www.ncbi.nlm.nih.gov/pubmed/37569432
http://dx.doi.org/10.3390/ijms241512052
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author Wear, Darcy
Bhagirath, Eesha
Balachandar, Arpana
Vegh, Caleb
Pandey, Siyaram
author_facet Wear, Darcy
Bhagirath, Eesha
Balachandar, Arpana
Vegh, Caleb
Pandey, Siyaram
author_sort Wear, Darcy
collection PubMed
description Neuroblastoma is the most common tumour in children under 1 year old, accounting for 12–15% of childhood cancer deaths. Although current treatments are relatively efficacious against this cancer, associated adverse effects could be detrimental to growth and development. In contrast, glioblastoma accounts for 52% of brain tumours and has an extremely poor prognosis. Current chemotherapeutics include temozolomide, which has numerous negative side-effects and a low-effective rate. Previous studies have shown the manipulation of autophagy to be a promising method for targeting cancers, including glioblastoma. We sought to determine the effects of autophagic alterations in combination with current chemotherapies in both neuroblastoma and glioblastoma. Supplementing cisplatin or temozolomide with autophagy activator rapamycin stabilized cancer cell mitochondria, despite having little effect on apoptosis or oxidative stress. Autophagy inhibition via 3-methyladenine or hydroxychloroquine alongside standard chemotherapies enhanced apoptosis and oxidative stress, with 3-methyladenine also disrupting mitochondrial health. Importantly, combining hydroxychloroquine with 0.5 µM cisplatin or 50 µg/mL temozolomide was as or more effective than 2 µM cisplatin or 100 µg/mL temozolomide alone. Analyzing these interesting results, a combined treatment of autophagy inhibitor with a standard chemotherapeutic agent could help to improve patient prognosis and reduce chemotherapy doses and their associated side-effects.
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spelling pubmed-104184532023-08-12 Autophagy Inhibition via Hydroxychloroquine or 3-Methyladenine Enhances Chemotherapy-Induced Apoptosis in Neuro-Blastoma and Glioblastoma Wear, Darcy Bhagirath, Eesha Balachandar, Arpana Vegh, Caleb Pandey, Siyaram Int J Mol Sci Article Neuroblastoma is the most common tumour in children under 1 year old, accounting for 12–15% of childhood cancer deaths. Although current treatments are relatively efficacious against this cancer, associated adverse effects could be detrimental to growth and development. In contrast, glioblastoma accounts for 52% of brain tumours and has an extremely poor prognosis. Current chemotherapeutics include temozolomide, which has numerous negative side-effects and a low-effective rate. Previous studies have shown the manipulation of autophagy to be a promising method for targeting cancers, including glioblastoma. We sought to determine the effects of autophagic alterations in combination with current chemotherapies in both neuroblastoma and glioblastoma. Supplementing cisplatin or temozolomide with autophagy activator rapamycin stabilized cancer cell mitochondria, despite having little effect on apoptosis or oxidative stress. Autophagy inhibition via 3-methyladenine or hydroxychloroquine alongside standard chemotherapies enhanced apoptosis and oxidative stress, with 3-methyladenine also disrupting mitochondrial health. Importantly, combining hydroxychloroquine with 0.5 µM cisplatin or 50 µg/mL temozolomide was as or more effective than 2 µM cisplatin or 100 µg/mL temozolomide alone. Analyzing these interesting results, a combined treatment of autophagy inhibitor with a standard chemotherapeutic agent could help to improve patient prognosis and reduce chemotherapy doses and their associated side-effects. MDPI 2023-07-27 /pmc/articles/PMC10418453/ /pubmed/37569432 http://dx.doi.org/10.3390/ijms241512052 Text en © 2023 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
Wear, Darcy
Bhagirath, Eesha
Balachandar, Arpana
Vegh, Caleb
Pandey, Siyaram
Autophagy Inhibition via Hydroxychloroquine or 3-Methyladenine Enhances Chemotherapy-Induced Apoptosis in Neuro-Blastoma and Glioblastoma
title Autophagy Inhibition via Hydroxychloroquine or 3-Methyladenine Enhances Chemotherapy-Induced Apoptosis in Neuro-Blastoma and Glioblastoma
title_full Autophagy Inhibition via Hydroxychloroquine or 3-Methyladenine Enhances Chemotherapy-Induced Apoptosis in Neuro-Blastoma and Glioblastoma
title_fullStr Autophagy Inhibition via Hydroxychloroquine or 3-Methyladenine Enhances Chemotherapy-Induced Apoptosis in Neuro-Blastoma and Glioblastoma
title_full_unstemmed Autophagy Inhibition via Hydroxychloroquine or 3-Methyladenine Enhances Chemotherapy-Induced Apoptosis in Neuro-Blastoma and Glioblastoma
title_short Autophagy Inhibition via Hydroxychloroquine or 3-Methyladenine Enhances Chemotherapy-Induced Apoptosis in Neuro-Blastoma and Glioblastoma
title_sort autophagy inhibition via hydroxychloroquine or 3-methyladenine enhances chemotherapy-induced apoptosis in neuro-blastoma and glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418453/
https://www.ncbi.nlm.nih.gov/pubmed/37569432
http://dx.doi.org/10.3390/ijms241512052
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