Evidence map›Paper›PMID 33177555›Full record

ArticleScientific reports2020

Structures of the free and inhibitors-bound forms of bromelain and ananain from Ananas comosus stem and in vitro study of their cytotoxicity.

Mohamed Azarkan, Erik Maquoi, François Delbrassine, Raphael Herman, Nasiha M'Rabet, Rafaèle Calvo Esposito, Paulette Charlier, Frédéric Kerff

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 22% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
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  15. Anacaulase-Bcdb for Enzymatic Eschar Removal in Adult and Paediatric Thermal Burns: Clinical Evidence, Safety, and Therapeutic Positioning.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
    Review
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

8 authors at 2 institutions in 1 country.

Mohamed AzarkanLaboratoire de Chimie Générale (Unité de Chimie Des Protéines), Faculté de Médecine, Université Libre de Bruxelles, Campus Erasme (CP 609), 1070, Bruxelles, Belgium. mazarkan@ulb.ac.be.
Erik MaquoiLaboratoire de Biologie Des Tumeurs Et du Développement, GIGA-Cancer, Université de Liège, 4000, Liège, Belgium.
François DelbrassineUR InBioS, Centre D'Ingénierie Des Protéines, Université de Liège, Sart Tilman, 4000, Liège, Belgium.
Raphael HermanUR InBioS, Centre D'Ingénierie Des Protéines, Université de Liège, Sart Tilman, 4000, Liège, Belgium.
Nasiha M'RabetLaboratoire de Chimie Générale (Unité de Chimie Des Protéines), Faculté de Médecine, Université Libre de Bruxelles, Campus Erasme (CP 609), 1070, Bruxelles, Belgium.
Rafaèle Calvo EspositoLaboratoire de Chimie Générale (Unité de Chimie Des Protéines), Faculté de Médecine, Université Libre de Bruxelles, Campus Erasme (CP 609), 1070, Bruxelles, Belgium.
Paulette CharlierUR InBioS, Centre D'Ingénierie Des Protéines, Université de Liège, Sart Tilman, 4000, Liège, Belgium.
Frédéric KerffUR InBioS, Centre D'Ingénierie Des Protéines, Université de Liège, Sart Tilman, 4000, Liège, Belgium. fkerff@uliege.be.
University of Liège · BEUniversité Libre de Bruxelles · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Ananas comosus stem extract is a complex mixture containing various cysteine ​​proteases of the C1A subfamily, such as bromelain and ananain. This mixture used for centuries in Chinese medicine, has several potential therapeutic applications as anti-cancer, anti-inflammatory and ecchymosis degradation agent. In the present work we determined the structures of bromelain and ananain, both in their free forms and in complex with the inhibitors E64 and TLCK. These structures combined with protease-substrate complexes modeling clearly identified the Glu68 as responsible for the high discrimination of bromelain in favor of substrates with positively charged residues at P2, and unveil the reasons for its weak inhibition by cystatins and E64. Our results with purified and fully active bromelain, ananain and papain show a strong reduction of cell proliferation with MDA-MB231 and A2058 cancer cell lines at a concentration of about 1 μM, control experiments clearly emphasizing the need for proteolytic activity. In contrast, while bromelain and ananain had a strong effect on the proliferation of the OCI-LY19 and HL-60 non-adherent cell lines, papain, the archetypal member of the C1A subfamily, had none. This indicates that, in this case, sequence/structure identity beyond the active site of bromelain and ananain is more important than substrate specificity.

Indexed as

AnanasAntineoplastic Agents, PhytogenicBromelainsCatalytic DomainCell Line, TumorCysteineCysteine EndopeptidasesCysteine Proteinase InhibitorsDisulfidesHumansLeucineModels, MolecularPlant StemsProtein ConformationSpectrometry, Mass, Electrospray IonizationSubstrate SpecificityananainAntineoplastic Agents, PhytogenicBromelainsCysteineCysteine EndopeptidasesCysteine Proteinase InhibitorsDisulfidesE 64Leucinestem bromelainTosyllysine Chloromethyl Ketone

Identifiers

PMID33177555
PMCPMC7658999
OpenAlexW3106267185

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.