Evidence map›Paper›PMID 30573560›Full record

ArticleJournal of lipid research2019

Multiple actions of doxorubicin on the sphingolipid network revealed by flux analysis.

Justin M Snider, Magali Trayssac, Christopher J Clarke, Nicholas Schwartz, Ashley J Snider, Lina M Obeid, Chiara Luberto, Yusuf A Hannun

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

19 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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  6. Upregulation of sphingosine kinase 1 in response to doxorubicin generates an angiogenic response via stabilization of Snail.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
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  8. Dihydroceramide desaturase 1 (DES1) promotes anchorage-independent survival downstream of HER2-driven glucose uptake and metabolism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
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  17. Ceramide launches an acute anti-adhesion pro-migration cell signaling program in response to chemotherapy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Justin M SniderMolecular and Cellular Biology and Biochemistry and Structural Biology Graduate Program, Stony Brook University, Stony Brook, NY; Departments of Medicine, Stony Brook University, Stony Brook, NY; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY.
Magali TrayssacDepartments of Medicine, Stony Brook University, Stony Brook, NY; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY.
Christopher J ClarkeDepartments of Medicine, Stony Brook University, Stony Brook, NY; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY.
Nicholas SchwartzDepartments of Medicine, Stony Brook University, Stony Brook, NY; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY.
Ashley J SniderDepartments of Medicine, Stony Brook University, Stony Brook, NY; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY; Northport Veterans Affairs Medical Center, Northport, NY.
Lina M ObeidDepartments of Medicine, Stony Brook University, Stony Brook, NY; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY; Northport Veterans Affairs Medical Center, Northport, NY.
Chiara LubertoStony Brook Cancer Center, Stony Brook University, Stony Brook, NY; Departments of Physiology and Biophysics, Stony Brook University, Stony Brook, NY. Electronic address: chiara.luberto@stonybrookmedicine.edu.
Yusuf A HannunDepartments of Medicine, Stony Brook University, Stony Brook, NY; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY; Departments of Biochemistry, Stony Brook University, Stony Brook, NY; Departments of Pharmacology, Stony Brook University, Stony Brook, NY; Departments of Pathology, Stony Brook University, Stony Brook, NY. Electronic address: yusuf.hannun@stonybrookmedicine.edu.
Stony Brook Medicine · USStony Brook University · US

Funding

Sphingolipids in Cancer Therapy and AngiogenesisP01CA097132 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI Daniel Canals · 2003 to 2026
$30.8M
Neutral Sphingomyelinases and Bioactive CeramidesR35GM118128 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI HANNUN, YUSUF AWNI · 2016 to 2025
$7.9M
Ceramide Activated Protein PhosphatasesR01CA218678 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI YUSUF AWNI HANNUN · 2018 to 2026
$3.4M
NCI NIH HHS P01 CA097132NCI NIH HHS R01 CA218678NIGMS NIH HHS R35 GM118128
6 · The paper itself

Abstract

Sphingolipids (SLs) have been implicated in numerous important cellular biologies; however, their study has been hindered by the complexities of SL metabolism. Furthermore, enzymes of SL metabolism represent a dynamic and interconnected network in which one metabolite can be transformed into other bioactive SLs through further metabolism, resulting in diverse cellular responses. Here we explore the effects of both lethal and sublethal doses of doxorubicin (Dox) in MCF-7 cells. The two concentrations of Dox resulted in the regulation of SLs, including accumulations in sphingosine, sphingosine-1-phosphate, dihydroceramide, and ceramide, as well as reduced levels of hexosylceramide. To further define the effects of Dox on SLs, metabolic flux experiments utilizing a d17 dihydrosphingosine probe were conducted. Results indicated the regulation of ceramidases and sphingomyelin synthase components specifically in response to the cytostatic dose. The results also unexpectedly demonstrated dose-dependent inhibition of dihydroceramide desaturase and glucosylceramide synthase in response to Dox. Taken together, this study uncovers novel targets in the SL network for the action of Dox, and the results reveal the significant complexity of SL response to even a single agent. This approach helps to define the role of specific SL enzymes, their metabolic products, and the resulting biologies in response to chemotherapeutics and other stimuli.

Indexed as

Metabolic Networks and PathwaysAntibiotics, AntineoplasticBiological TransportDose-Response Relationship, DrugDoxorubicinHumansMCF-7 CellsSphingolipidsStructure-Activity RelationshipTumor Cells, CulturedAntibiotics, AntineoplasticDoxorubicinSphingolipidschemotherapeutichigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometrymetabolism

Identifiers

PMID30573560
PMCPMC6446699
OpenAlexW2906118074

What OpenQuestion holds

Textmetadata
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.