Evidence map›Paper›PMID 23267130›Full record

ArticleAnticancer research2013

Dihydroceramide desaturase knockdown impacts sphingolipids and apoptosis after photodamage in human head and neck squamous carcinoma cells.

Paul Breen, Nicholas Joseph, Kyle Thompson, Jacqueline M Kraveka, Tatyana I Gudz, Li Li, Mehrdad Rahmaniyan, Jacek Bielawski, Jason S Pierce, Eric VAN Buren and 2 more

Abstract read
In one paragraph

Article in Anticancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
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

25 citing papers in PubMed.

  1. FASEB bioAdvances · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Sphingolipids in Atherosclerosis: Chimeras in Structure and Function.International journal of molecular sciences · 2022
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. The role of dihydrosphingolipids in disease.Cellular and molecular life sciences : CMLS · 2019
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

12 authors.

Paul BreenDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201, USA. dseparovic@wayne.edu
Nicholas Joseph
Kyle Thompson
Jacqueline M Kraveka
Tatyana I Gudz
Li Li
Mehrdad Rahmaniyan
Jacek Bielawski
Jason S Pierce
Eric VAN Buren
Gaurav Bhatti
Duska Separovic

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND N. DUBOIS · 2009 to 2026
$42.7M
Sphingolipids in Cancer Therapy and AngiogenesisP01CA097132 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI Daniel Canals · 2003 to 2026
$30.8M
THE ROLE OF LACTOSYLCERAMIDE IN RENAL AGING AND DISEASEP20RR017677 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MAO, CUNGUI · 2002 to 2011
$23.4M
EXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR018823 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND, JOHN R · 2003 to 2003
$2.9M
Sphingolipids in Cell Death after PhotodamageR01CA077475 · NCI · WAYNE STATE UNIVERSITY · PI SEPAROVIC, DUSKA M · 2005 to 2012
$1.6M
NCI NIH HHS IPO1CA097132NCI NIH HHS P01 CA097132NCI NIH HHS P30 CA 138313NCI NIH HHS P30 CA138313NCI NIH HHS R01 CA077475NCI NIH HHS R01 CA77475NCRR NIH HHS C06 RR018823NCRR NIH HHS C06RR018823NCRR NIH HHS P20 RR017677NCRR NIH HHS P20-RR17677
6 · The paper itself

Abstract

backgroundDihydroceramide desaturase 1 (DES) is the enzyme responsible for converting dihydroceramide into ceramide in the de novo sphingolipid biosynthesis pathway. Dihydroceramide can inhibit ceramide channel formation to interfere with apoptosis. We have shown that following ceramide synthase knockdown, photodynamic therapy (PDT), a cancer treatment modality, is associated with decreased levels of ceramides and dihydroceramides in cells that are resistant to apoptosis.

aimHere we investigated the effect of DES knockdown on the sphingolipid profile and apoptosis in human head and neck squamous carcinoma cells after PDT with the silicon phthalocyanine Pc 4. MATERIALS AND

methodsFollowing siRNA transfection and PDT treatment, quantitative real-time polymerase chain reaction for quantification of DES mRNA, immunoblotting for protein expression, mass spectrometry for sphingolipid analysis, spectrofluorometry for caspase 3-like (DEVDase) activity, flow cytometry for apoptosis detection, and trypan blue assay for cell viability evaluation, were performed.

resultsDown-regulation of DES led to a substantial increase in levels of dihydroceramides without affecting ceramide levels. PDT-induced accumulation of individual dihydroceramides and global ceramides was increased by DES knockdown. Concomitantly, mitochondrial depolarization, DEVDase activation, late-apoptosis and cell death were attenuated by DES knockdown. Early apoptosis, however, was enhanced.

conclusionOur findings support the following: (i) dihydroceramide reduces pro-apoptotic effects of ceramide; (ii) cells adapt to DES knockdown to become more sensitive to ceramide and early-apoptosis; (iii) DES is a potential molecular target for regulating apoptotic resistance to PDT.

Indexed as

Carcinoma, Squamous CellHead and Neck NeoplasmsOxidoreductasesPhotochemotherapyApoptosisCell Line, TumorCeramidesGene Expression Regulation, NeoplasticHumansIndolesMolecular Targeted TherapyRNA, Small InterferingSphingolipidsCeramidesdihydroceramidedihydroceramide desaturaseIndolesOxidoreductasesphthalocyanine Pc 4RNA, Small InterferingSphingolipids

Identifiers

PMID23267130
PMCPMC3905466

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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.