PMID- 37185742 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230517 IS - 1467-3045 (Electronic) IS - 1467-3037 (Print) IS - 1467-3037 (Linking) VI - 45 IP - 4 DP - 2023 Apr 11 TI - The Involvement of Hypoxia in the Response of Neuroblastoma Cells to the Exposure of Atorvastatin. PG - 3333-3346 LID - 10.3390/cimb45040218 [doi] AB - 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 (CoCl(2)) and with or without echinomycin (HIF-1alpha 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. FAU - Correia, Ana Salome AU - Correia AS AUID- ORCID: 0000-0002-8231-1560 AD - OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Placido da Costa, 4200-450 Porto, Portugal. AD - Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. AD - CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernani Monteiro, 4200-319 Porto, Portugal. FAU - Marques, Lara AU - Marques L AUID- ORCID: 0000-0002-7003-4957 AD - OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Placido da Costa, 4200-450 Porto, Portugal. AD - CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernani Monteiro, 4200-319 Porto, Portugal. FAU - Vale, Nuno AU - Vale N AUID- ORCID: 0000-0002-1283-1042 AD - OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Placido da Costa, 4200-450 Porto, Portugal. AD - CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernani Monteiro, 4200-319 Porto, Portugal. AD - Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine, University of Porto, Alameda Professor Hernani Monteiro, 4200-319 Porto, Portugal. LA - eng PT - Journal Article DEP - 20230411 PL - Switzerland TA - Curr Issues Mol Biol JT - Current issues in molecular biology JID - 100931761 PMC - PMC10137104 OTO - NOTNLM OT - atorvastatin OT - drug repurposing OT - echinomycin OT - hypoxia-inducible factor-1 OT - neuroblastoma cells COIS- The authors declare no conflict of interest. EDAT- 2023/05/15 19:12 MHDA- 2023/05/15 19:13 PMCR- 2023/04/11 CRDT- 2023/05/15 13:46 PHST- 2023/03/02 00:00 [received] PHST- 2023/03/31 00:00 [revised] PHST- 2023/04/05 00:00 [accepted] PHST- 2023/05/15 19:13 [medline] PHST- 2023/05/15 19:12 [pubmed] PHST- 2023/05/15 13:46 [entrez] PHST- 2023/04/11 00:00 [pmc-release] AID - cimb45040218 [pii] AID - cimb-45-00218 [pii] AID - 10.3390/cimb45040218 [doi] PST - epublish SO - Curr Issues Mol Biol. 2023 Apr 11;45(4):3333-3346. doi: 10.3390/cimb45040218.