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The Involvement of Hypoxia in the Response of Neuroblastoma Cells to the Exposure of Atorvastatin

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Title: The Involvement of Hypoxia in the Response of Neuroblastoma Cells to the Exposure of Atorvastatin
Authors: Ana Salomé Correia, Lara Marques, Nuno Vale
Source: Current Issues in Molecular Biology, Vol 45, Iss 4, Pp 3333-3346 (2023)
Publisher Information: MDPI AG, 2023.
Publication Year: 2023
Collection: LCC:Biology (General)
Subject Terms: drug repurposing, atorvastatin, neuroblastoma cells, hypoxia-inducible factor-1, echinomycin, Biology (General), QH301-705.5
More Details: Cancer is a set of complex diseases, being one of the leading causes of death worldwide. Despite a lot of research on the molecular pathways and effective treatments, there are still huge gaps. Indeed, the development of new anti-cancer drugs is a complex process. To face this problem, drug repurposing is being increasingly applied. This approach aims to identify new indications for already approved drugs. In this regard, statins (clinically used for reducing cholesterol levels) are reported to induce anti-cancer effects, particularly by inducing apoptosis and altering the tumor microenvironment. Atorvastatin is a type of statin with several potentialities as an anti-cancer agent, supported by several studies. Our study aimed to explore the effect of this drug in SH-SY5Y human neuroblastoma cells. Additionally, we also aimed to understand how this drug acts under hypoxia and the inhibition of hypoxia-inducible factor-1 (HIF-1). For that purpose, we assessed cellular viability/morphology after exposure to different concentrations of atorvastatin, with or without chemically induced hypoxia with chloride cobalt (CoCl2) and with or without echinomycin (HIF-1α inhibitor). Our results supported the cytotoxic effects of atorvastatin. Additionally, we also revealed that besides these effects, under hypoxia, this drug induced proliferation of the neuroblastoma cells, supporting the importance of different stimuli and environment on the effect of drugs on cancer cells.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1467-3045
1467-3037
Relation: https://www.mdpi.com/1467-3045/45/4/218; https://doaj.org/toc/1467-3037; https://doaj.org/toc/1467-3045
DOI: 10.3390/cimb45040218
Access URL: https://doaj.org/article/bd6f3061cbda4348bd403d29f4d397fe
Accession Number: edsdoj.bd6f3061cbda4348bd403d29f4d397fe
Database: Directory of Open Access Journals
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  Data: Current Issues in Molecular Biology, Vol 45, Iss 4, Pp 3333-3346 (2023)
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  Data: Cancer is a set of complex diseases, being one of the leading causes of death worldwide. Despite a lot of research on the molecular pathways and effective treatments, there are still huge gaps. Indeed, the development of new anti-cancer drugs is a complex process. To face this problem, drug repurposing is being increasingly applied. This approach aims to identify new indications for already approved drugs. In this regard, statins (clinically used for reducing cholesterol levels) are reported to induce anti-cancer effects, particularly by inducing apoptosis and altering the tumor microenvironment. Atorvastatin is a type of statin with several potentialities as an anti-cancer agent, supported by several studies. Our study aimed to explore the effect of this drug in SH-SY5Y human neuroblastoma cells. Additionally, we also aimed to understand how this drug acts under hypoxia and the inhibition of hypoxia-inducible factor-1 (HIF-1). For that purpose, we assessed cellular viability/morphology after exposure to different concentrations of atorvastatin, with or without chemically induced hypoxia with chloride cobalt (CoCl2) and with or without echinomycin (HIF-1α inhibitor). Our results supported the cytotoxic effects of atorvastatin. Additionally, we also revealed that besides these effects, under hypoxia, this drug induced proliferation of the neuroblastoma cells, supporting the importance of different stimuli and environment on the effect of drugs on cancer cells.
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      – SubjectFull: atorvastatin
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      – SubjectFull: neuroblastoma cells
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