Evidence map›Paper›PMID 19549337›Full record

ArticleMolecular cancer2009

Effects of cIAP-1, cIAP-2 and XIAP triple knockdown on prostate cancer cell susceptibility to apoptosis, cell survival and proliferation.

Catherine Gill, Catherine Dowling, Amanda J O'Neill, R William G Watson

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

38 citing papers in PubMed, 77 citations in OpenAlex.

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  10. Pro-Survival Factor EDEM3 Confers Therapy Resistance in Prostate Cancer.International journal of molecular sciences · 2022
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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

4 authors at 1 institution in 1 country.

Catherine GillUCD School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. cgill@hrb.ie
Catherine Dowling
Amanda J O'Neill
R William G Watson
University College Dublin · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundManipulating apoptotic resistance represents an important strategy for the treatment of hormone refractory prostate cancer. We hypothesised that the Inhibitor of Apoptosis (IAP) Proteins may be mediating this resistance and knockdown of cIAP-1, cIAP-2 and XIAP would increase sensitivity to apoptosis.

methodscIAP-1, cIAP-2 and XIAP where knocked down either individually or in combination using siRNA in androgen independent prostate cancer PC-3 cells as confirmed by real-time PCR and western blotting. Cells were then treated with TRAIL, Etoposide, or Tunicamycin, and apoptosis assessed by PI DNA staining. Apoptosis was confirmed with Annexin V labelling and measurement of PARP cleavage, and was inhibited using the pan-caspase inhibitor, zVAD.fmk. Clonogenic assays and assessment of ID-1 expression by western blotting were used to measure recovery and proliferation.

resultsPC-3 are resistant to TRAIL induced apoptosis and have elevated expression of cIAP-1, cIAP-2 and XIAP. Combined knockdown sensitised PC-3 to TRAIL induced apoptosis, but not to Etoposide or Tunicmycin, with corresponding increases in caspase activity and PARP cleavage which was inhibited by ZVAD.fmk. Triple knock down decreased proliferation which was confirmed by decreased ID-1 expression.

conclusionSimultaneous knock down of the IAPs not only sensitised the PC-3 to TRAIL but also inhibited their proliferation rates and clonogenic survival. The inability to alter sensitivity to other triggers of apoptosis suggests that this effect is specific for death receptor pathways and knock down might facilitate immune-surveillance mechanisms to counter cancer progression and, in combination with therapeutic approaches using TRAIL, could represent an important treatment strategy.

Indexed as

ApoptosisCell ProliferationCell SurvivalBaculoviral IAP Repeat-Containing 3 ProteinCell Line, TumorData Interpretation, StatisticalEtoposideGene ExpressionGene Knockdown TechniquesHumansInhibitor of Apoptosis ProteinsMalePeptide HydrolasesProstatic NeoplasmsRNA, Small InterferingTNF-Related Apoptosis-Inducing LigandBaculoviral IAP Repeat-Containing 3 ProteinBIRC3 protein, humanDEVDaseEtoposideInhibitor of Apoptosis ProteinsPeptide HydrolasesRNA, Small InterferingTNF-Related Apoptosis-Inducing LigandTunicamycinUbiquitin-Protein LigasesXIAP protein, humanX-Linked Inhibitor of Apoptosis Protein

Identifiers

PMID19549337
PMCPMC2706796
OpenAlexW2112513860

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.