Evidence map›Paper›PMID 29948946›Full record

ArticleMolecular neurobiology2019

Heme Oxygenase Inhibition Sensitizes Neuroblastoma Cells to Carfilzomib.

Ignazio Barbagallo, Cesarina Giallongo, Giovanni Li Volti, Alfio Distefano, Giuseppina Camiolo, Marco Raffaele, Loredana Salerno, Valeria Pittalà, Valeria Sorrenti, Roberto Avola and 4 more

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Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 28 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Ignazio BarbagalloDepartment of Drug Science, Biochemistry Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
Cesarina GiallongoDepartment of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia, 97, 95125, Catania, Italy. cesarinagiallongo@yahoo.it.ORCID http://orcid.org/0000-0002-7667-6088
Giovanni Li VoltiDepartment of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia, 97, 95125, Catania, Italy.
Alfio DistefanoDepartment of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia, 97, 95125, Catania, Italy.
Giuseppina CamioloDepartment of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia, 97, 95125, Catania, Italy.
Marco RaffaeleDepartment of Drug Science, Biochemistry Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
Loredana SalernoDepartment of Drug Science, Biochemistry Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
Valeria PittalàDepartment of Drug Science, Biochemistry Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
Valeria SorrentiDepartment of Drug Science, Biochemistry Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
Roberto AvolaDepartment of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia, 97, 95125, Catania, Italy.
Michelino Di RosaDepartment of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia, 97, 95125, Catania, Italy.
Luca VanellaDepartment of Drug Science, Biochemistry Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
Francesco Di RaimondoDepartment of Surgery, Medical and Surgical Specialties, University of Catania, Via Santa Sofia, 78, 95123, Catania, Italy.
Daniele TibulloDepartment of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia, 97, 95125, Catania, Italy.
University of Catania · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuroblastoma (NB) is an embryonic malignancy affecting the physiological development of adrenal medulla and paravertebral sympathetic ganglia in early infancy. Proteasome inhibitors (PIs) (i.e., carfilzomib (CFZ)) may represent a possible pharmacological treatment for solid tumors including NB. In the present study, we tested the effect of a novel non-competitive inhibitor of heme oxygenase-1 (HO-1), LS1/71, as a possible adjuvant therapy for the efficacy of CFZ in neuroblastoma cells. Our results showed that CFZ increased both HO-1 gene expression (about 18-fold) and HO activity (about 8-fold), following activation of the ER stress pathway. The involvement of HO-1 in CFZ-mediated cytotoxicity was further confirmed by the protective effect of pharmacological induction of HO-1, significantly attenuating cytotoxicity. In addition, HO-1 selective inhibition by a specific siRNA increased the cytotoxic effect following CFZ treatment in NB whereas SnMP, a competitive pharmacological inhibitor of HO, showed no changes in cytotoxicity. Our data suggest that treatment with CFZ produces ER stress in NB without activation of CHOP-mediated apoptosis, whereas co-treatment with CFZ and LS1/71 led to apoptosis activation and CHOP expression induction. In conclusion, our study showed that treatment with the non-competitive inhibitor of HO-1, LS1 / 71, increased cytotoxicity mediated by CFZ, triggering apoptosis following ER stress activation. These results suggest that PIs may represent a possible pharmacological treatment for solid tumors and that HO-1 inhibition may represent a possible strategy to overcome chemoresistance and increase the efficacy of chemotherapic regimens.

Indexed as

Antineoplastic AgentsApoptosisCell Line, TumorCell SurvivalDrug Resistance, NeoplasmHeme Oxygenase (Decyclizing)HumansNeuroblastomaOligopeptidesProteasome InhibitorsAntineoplastic AgentscarfilzomibHeme Oxygenase (Decyclizing)OligopeptidesProteasome InhibitorsCarfilzomibHeme oxygenaseInhibitorsNeuroblastomaProteasome

Identifiers

PMID29948946
OpenAlexW2806833134

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.