Evidence map›Paper›PMID 36697631›Full record

ArticleCommunications chemistry2021

Landomycins as glutathione-depleting agents and natural fluorescent probes for cellular Michael adduct-dependent quinone metabolism.

Alessio Terenzi, Mery La Franca, Sushilla van Schoonhoven, Rostyslav Panchuk, Álvaro Martínez, Petra Heffeter, Redding Gober, Christine Pirker, Petra Vician, Christian R Kowol and 4 more

Open access · goldAbstract read
In one paragraph

Article in Communications chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.7field-weighted citation impact, top 18% 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

5 citing papers in PubMed, 12 citations in OpenAlex.

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  5. Targeted Isolation ofACS omega · 2023
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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 7 institutions in 5 countries.

Alessio TerenziDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Viale delle Scienze, Ed. 17, 90128, Palermo, Italy.ORCID http://orcid.org/0000-0001-9751-1373
Mery La FrancaDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Viale delle Scienze, Ed. 17, 90128, Palermo, Italy.
Sushilla van SchoonhovenInstitute of Cancer Research and Comprehensive Cancer Center, Medical University Vienna, Spitalgasse 23, 1090, Vienna, Austria.
Rostyslav PanchukDepartment of Regulation of Cell Proliferation and Apoptosis, Institute of Cell Biology, Drahomanov St., 14/16, Lviv, 79005, Ukraine.
Álvaro MartínezDonostia International Physics Center and Polimero eta Material Aurreratuak: Fisika, Kimika eta Teknologia, Kimika Fakultatea, Euskal Herriko Unibertsitatea UPV/EHU, Paseo Manuel de Lardizabal 4, Donostia, 20018, Spain.
Petra HeffeterInstitute of Cancer Research and Comprehensive Cancer Center, Medical University Vienna, Spitalgasse 23, 1090, Vienna, Austria.
Redding GoberCollege of Pharmacy, University of Kentucky, South Limestone Str. 789, Lexington, 40536-0596, USA.
Christine PirkerInstitute of Cancer Research and Comprehensive Cancer Center, Medical University Vienna, Spitalgasse 23, 1090, Vienna, Austria.
Petra VicianInstitute of Cancer Research and Comprehensive Cancer Center, Medical University Vienna, Spitalgasse 23, 1090, Vienna, Austria.
Christian R KowolResearch Cluster "Translational Cancer Therapy Research", University of Vienna and Medical University of Vienna, Vienna, Austria.
Rostyslav StoikaDepartment of Regulation of Cell Proliferation and Apoptosis, Institute of Cell Biology, Drahomanov St., 14/16, Lviv, 79005, Ukraine.
Luca SalassaDonostia International Physics Center and Polimero eta Material Aurreratuak: Fisika, Kimika eta Teknologia, Kimika Fakultatea, Euskal Herriko Unibertsitatea UPV/EHU, Paseo Manuel de Lardizabal 4, Donostia, 20018, Spain.
Jürgen RohrCollege of Pharmacy, University of Kentucky, South Limestone Str. 789, Lexington, 40536-0596, USA.
Walter BergerInstitute of Cancer Research and Comprehensive Cancer Center, Medical University Vienna, Spitalgasse 23, 1090, Vienna, Austria. walter.berger@meduniwien.ac.at.ORCID http://orcid.org/0000-0003-0014-1658
Comprehensive Cancer Center Vienna · ATInstitute of Cell Biology · UAUniversity of Kentucky · USIkerbasque · ESUniversity of Palermo · ITUniversity of the Basque Country · ESUniversity of Vienna · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Landomycins are angucyclines with promising antineoplastic activity produced by Streptomyces bacteria. The aglycone landomycinone is the distinctive core, while the oligosaccharide chain differs within derivatives. Herein, we report that landomycins spontaneously form Michael adducts with biothiols, including reduced cysteine and glutathione, both cell-free or intracellularly involving the benz[a]anthraquinone moiety of landomycinone. While landomycins generally do not display emissive properties, the respective Michael adducts exerted intense blue fluorescence in a glycosidic chain-dependent manner. This allowed label-free tracking of the short-lived nature of the mono-SH-adduct followed by oxygen-dependent evolution with addition of another SH-group. Accordingly, hypoxia distinctly stabilized the fluorescent mono-adduct. While extracellular adduct formation completely blocked the cytotoxic activity of landomycins, intracellularly it led to massively decreased reduced glutathione levels. Accordingly, landomycin E strongly synergized with glutathione-depleting agents like menadione but exerted reduced activity under hypoxia. Summarizing, landomycins represent natural glutathione-depleting agents and fluorescence probes for intracellular anthraquinone-based angucycline metabolism.

Identifiers

PMID36697631
PMCPMC9814637
OpenAlexW3216927687

What OpenQuestion holds

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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.