Evidence map›Paper›PMID 12082550›Full record

ArticleNeoplasia (New York, N.Y.)

Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas.

Jim Dimitroulakos, Wilson H Marhin, Jason Tokunaga, Jonathan Irish, Patrick Gullane, Linda Z Penn, Suzanne Kamel-Reid

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neoplasia (New York, N.Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 6 pooled it
2.2field-weighted citation impact, top 12% 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

40 citing papers in PubMed, 6 syntheses or guidelines pooled it, 98 citations in OpenAlex.

  1. Pooled it
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  6. Pooled it
  7. Article
  8. The emerging role of cholesterol metabolism in gynecologic cancer development and therapy.Apoptosis : an international journal on programmed cell death · 2026
    Review
  9. Article
  10. Article
  11. Article
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  13. Review
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  16. Pleiotropic effects of statins: A focus on cancer.Biochimica et biophysica acta. Molecular basis of disease · 2020
    Review
  17. Review
  18. Review
  19. Article
  20. Statin Use After Diagnosis of Hepatocellular Carcinoma Is Associated With Decreased Mortality.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2019
    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

7 authors at 1 institution in 1 country.

Jim DimitroulakosDepartment of Cellular and Molecular Biology, The University Health Network, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
Wilson H Marhin
Jason Tokunaga
Jonathan Irish
Patrick Gullane
Linda Z Penn
Suzanne Kamel-Reid
University Health Network · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We recently identified 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme of the mevalonate pathway, as a potential therapeutic target of the head and neck squamous cell carcinomas (HNSCC) and cervical carcinomas (CC). The products of this complex biochemical pathway, including de novo cholesterol, are vital for a variety of key cellular functions affecting membrane integrity, cell signaling, protein synthesis, and cell cycle progression. Lovastatin, a specific inhibitor of HMG-CoA reductase, induces a pronounced apoptotic response in a specific subset of tumor types, including HNSCC and CC. The mediators of this response are not well established. Identification of differentially expressed genes represents a feasible approach to delineate these mediators as lovastatin has the potential to modulate transcription indirectly by perturbing levels of sterols and other mevalonate metabolites. Expression analysis following treatment of the HNSCC cell lines SCC9 or SCC25 with 10 microM lovastatin for 1 day showed that less than 2% (9 cDNAs) of the 588 cDNAs on this microarray were affected in both cell lines. These included diazepam-binding inhibitor/acyl-CoA-binding protein, the activated transcription factor 4 and rhoA. Because the biosynthesis of mevalonate leads to its incorporation into more than a dozen classes of end products, their role in lovastatin-induced apoptosis was also evaluated. Addition of the metabolites of all the major branches of the mevalonate pathway indicated that only the nonsterol moiety, geranylgeranyl pyrophosphate (GGPP), significantly inhibited the apoptotic effects of lovastatin in HNSCC and CC cells. Because rhoA requires GGPP for its function, this links the microarray and biochemical data and identifies rhoA as a potential mediator of the anticancer properties of lovastatin. Our data suggest that the depletion of nonsterol mevalonate metabolites, particularly GGPP, can be potential mediators of lovastatin-induced apoptosis of HNSCC and CC cells.

Indexed as

DNA FingerprintingOligonucleotide Array Sequence AnalysisActivating Transcription FactorsAnimalsApoptosisBlood ProteinsBlotting, WesternCarcinoma, Squamous CellCCAAT-Enhancer-Binding ProteinsCell SurvivalChlorocebus aethiopsCholesterolCoenzyme A LigasesConsensus SequenceCOS CellsDiazepam Binding InhibitorActivating Transcription FactorsBlood ProteinsCCAAT-Enhancer-Binding ProteinsCholesterolCoenzyme A LigasesDiazepam Binding InhibitorDNA-Binding ProteinsFluorescent Dyesgeranylgeranyl pyrophosphateHydroxymethylglutaryl-CoA Reductase InhibitorsHydroxymethylglutaryl CoA ReductasesHydroxymethylglutaryl-CoA SynthaseLovastatinLuciferasesMevalonic AcidNeoplasm ProteinsPhalloidinePolyisoprenyl PhosphatesRecombinant Fusion ProteinsrhoA GTP-Binding ProteinSREBF1 protein, humanSterol Regulatory Element Binding Protein 1SterolsTranscription Factors

Identifiers

PMID12082550
PMCPMC1531704
OpenAlexW2091612622

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.