Evidence map›Paper›PMID 26900800›Full record

ArticleCell cycle (Georgetown, Tex.)2016

Combining p53 stabilizers with metformin induces synergistic apoptosis through regulation of energy metabolism in castration-resistant prostate cancer.

Long Chen, Nihal Ahmad, Xiaoqi Liu

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

Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

24 citing papers in PubMed, 32 citations in OpenAlex.

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  6. Metformin in overcoming enzalutamide resistance in castration-resistant prostate cancer.The Journal of pharmacology and experimental therapeutics · 2025
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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

3 authors at 3 institutions in 1 country.

Long Chena Department of Biochemistry , Purdue University , West Lafayette , IN , USA.
Nihal Ahmadb Department of Dermatology , University of Wisconsin , Madison , WI , USA.
Xiaoqi Liua Department of Biochemistry , Purdue University , West Lafayette , IN , USA.
Center for Cancer Research · USPurdue University West Lafayette · USUniversity of Wisconsin–Madison · US

Funding

Role of Polo-Like Kinase-1 in Melanocytic TransformationR01AR059130 · NIAMS · UNIVERSITY OF WISCONSIN-MADISON · PI AHMAD, NIHAL · 2010 to 2019
$3.8M
Enhancing anti-neoplastic activity of metformin in prostate cancerR01CA192894 · NCI · UNIVERSITY OF KENTUCKY · PI LIU, XIAOQI · 2016 to 2020
$1.7M
Role of SIRT1 in melanocyte biology and melanocyte transformationR01CA176748 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AHMAD, NIHAL · 2013 to 2017
$1.6M
NCI NIH HHS R01 CA176748NCI NIH HHS R01 CA192894NIAMS NIH HHS R01 AR059130
6 · The paper itself

Abstract

Since altered energy metabolism is a hallmark of cancer, many drugs targeting metabolic pathways are in active clinical trials. The tumor suppressor p53 is often inactivated in cancer, either through downregulation of protein or loss-of-function mutations. As such, stabilization of p53 is considered as one promising approach to treat those cancers carrying wild type (WT) p53. Herein, SIRT1 inhibitor Tenovin-1 and polo-like kinase 1 (Plk1) inhibitor BI2536 were used to stabilize p53. We found that both Tennovin-1 and BI2536 increased the anti-neoplastic activity of metformin, an inhibitor of oxidative phosphorylation, in a p53 dependent manner. Since p53 has also been shown to regulate metabolic pathways, we further analyzed glycolysis and oxidative phosphorylation upon drug treatments. We showed that both Tennovin-1 and BI2536 rescued metformin-induced glycolysis and that both Tennovin-1 and BI2536 potentiated metformin-associated inhibition of oxidative phosphorylation. Of significance, castration-resistant prostate cancer (CRPC) C4-2 cells show a much more robust response to the combination treatment than the parental androgen-dependent prostate cancer LNCaP cells, indicating that targeting energy metabolism with metformin plus p53 stabilizers might be a valid approach to treat CRPC carrying WT p53.

Indexed as

Gene Expression Regulation, NeoplasticAcetanilidesAntineoplastic AgentsApoptosisCell Cycle ProteinsCell Line, TumorDrug SynergismDrug Therapy, CombinationGlycolysisHumansMaleMetforminMitochondriaMitosisOxidative PhosphorylationPolo-Like Kinase 1AcetanilidesAntineoplastic AgentsBI 2536Cell Cycle ProteinsMetforminPolo-Like Kinase 1Protein Serine-Threonine KinasesProto-Oncogene ProteinsPteridinesSIRT1 protein, humanSirtuin 1tenovin-1ThioureaTumor Suppressor Protein p53BI2536glycolysismetforminoxidative phosphorylationp53Plk1SIRT1Tenovin-1

Identifiers

PMID26900800
PMCPMC4845973
OpenAlexW2286516112

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.