Evidence map›Paper›PMID 25880275›Full record

ArticleScientific reports2015

Nelfinavir and nelfinavir analogs block site-2 protease cleavage to inhibit castration-resistant prostate cancer.

Min Guan, Leila Su, Yate-Ching Yuan, Haiqing Li, Warren A Chow

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

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

42 citing papers in PubMed, 60 citations in OpenAlex.

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  14. Key events in cancer: Dysregulation of SREBPs.Frontiers in pharmacology · 2023
    Review
  15. Targeting lipid metabolism in metastatic prostate cancer.Therapeutic advances in medical oncology · 2023
    Review
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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

5 authors at 2 institutions in 1 country.

Min GuanDepartment of Molecular Pharmacology, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
Leila SuDepartment of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
Yate-Ching YuanDepartment of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
Haiqing LiDepartment of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
Warren A Chow1] Department of Molecular Pharmacology, Beckman Research Institute of the City of Hope, Duarte, CA, USA [2] Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
City of Hope · USBeckman Research Institute

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nelfinavir and its analogs inhibit proliferation and induce apoptosis of castration-resistant prostate cancer through inhibition of site-2 protease (S2P) activity, which leads to suppression of regulated intramembrane proteolysis. Western blotting in nelfinavir and its analog treated cells confirms accumulation of precursor SREBP-1 and ATF6. Nelfinavir and its analogs inhibit human homolog M. jannaschii S2P cleavage of an artificial protein substrate CED-9 in an in vitro proteolysis assay in a dose-dependent manner. Nelfinavir and its analogs are more potent inhibitors of S2P cleavage activity than 1,10-phenanthroline, a metalloprotease-specific inhibitor. Further, cluster analysis of gene expression from treated DU145 and PC3 cell lines demonstrate a close similarity of nelfinavir, its analogs, and 1,10-phenanthroline. These results show nelfinavir and its analogs inhibit castration-resistant prostate cancer proliferation by blocking regulated intramembrane proteolysis through suppression of S2P cleavage activity. This leads to accumulation of precursor SREBP-1 and ATF6, and development of insufficient reserves of their transcriptionally-active forms. The present results validate S2P and regulated intramembrane proteolysis as novel therapeutic targets for castration-resistant prostate cancer therapeutics. A clinical trial of nelfinavir or its analogs should be developed for castration-resistant prostate cancer.

Indexed as

Activating Transcription Factor 6ApoptosisCell Line, TumorCell ProliferationCluster AnalysisHumansMaleMetalloendopeptidasesMethanocaldococcaceaeNelfinavirProstatic Neoplasms, Castration-ResistantProtein PrecursorsProteolysisProto-Oncogene Proteins c-bcl-2RNASequence Analysis, RNAActivating Transcription Factor 6ATF6 protein, humanMBTPS2 protein, humanMetalloendopeptidasesNelfinavirProtein PrecursorsProto-Oncogene Proteins c-bcl-2RNASREBF1 protein, humanSterol Regulatory Element Binding Protein 1

Identifiers

PMID25880275
PMCPMC4816264
OpenAlexW2005975551

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.