Evidence map›Paper›PMID 39793570›Full record

ArticleCell reports. Medicine2025

Mitochondrial uncouplers inhibit oncogenic E2F1 activity and prostate cancer growth.

Ohuod Hawsawi, Weinan Xue, Tingting Du, Mengqi Guo, Xiaolin Yu, Mingyi Zhang, Paul S Hoffman, Roni Bollag, Jun Li, Jia Zhou and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Molecular and cellular mechanisms of pentadecanoic acid.World journal of biological chemistry · 2025
    Review
  4. Review
  5. Review
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

15 authors.

Ohuod HawsawiGeorgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
Weinan XueGeorgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
Tingting DuGeorgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Institute of Materia Medica, Peking Union Medical College, Beijing 100050, China.
Mengqi GuoGeorgia Cancer Center, Augusta University, Augusta, GA 30912, USA; College of Pharmacy, Yantai University, Yantai, Shandong Province 264005, China.
Xiaolin YuGeorgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
Mingyi ZhangGeorgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Institute of Materia Medica, Peking Union Medical College, Beijing 100050, China.
Paul S HoffmanDivision of Infectious Diseases & International Health, University of Virginia, Charlottesville, VA 22903, USA.
Roni BollagGeorgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
Jun LiDepartment of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Jia ZhouDepartment of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Hongbo WangCollege of Pharmacy, Yantai University, Yantai, Shandong Province 264005, China.
Junran ZhangDepartment of Radiation Oncology, Ohio State University, Columbus, OH 43210, USA.
Zheng FuInstitute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Xiaoguang ChenInstitute of Materia Medica, Peking Union Medical College, Beijing 100050, China.
Chunhong YanGeorgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. Electronic address: cyan@augusta.edu.

Funding

ATF3 Regulation of Histone Acetylation in Genome MaintenanceR01CA240966 · NCI · AUGUSTA UNIVERSITY · PI YAN, CHUNHONG · 2020 to 2025
$1.7M
NCI NIH HHS R01 CA240966
6 · The paper itself

Abstract

Mitochondrial uncouplers dissipate proton gradients and deplete ATP production from oxidative phosphorylation (OXPHOS). While the growth of prostate cancer depends on OXPHOS-generated ATP, the oncogenic pathway mediated by the transcription factor E2F1 is crucial for the progression of this deadly disease. Here, we report that mitochondrial uncouplers, including tizoxanide (TIZ), the active metabolite of the Food and Drug Administration (FDA)-approved anthelmintic nitazoxanide (NTZ), inhibit E2F1-mediated expression of genes involved in cell cycle progression, DNA synthesis, and lipid synthesis. Consequently, NTZ/TIZ induces S-phase kinase-associated protein 2 (SKP2)-mediated G1 arrest while impeding DNA synthesis, lipogenesis, and the growth of prostate cancer cells. The anti-cancer activity of TIZ correlates with its OXPHOS-uncoupling activity. NTZ/TIZ appears to inhibit ATP production, thereby activating the AMP-activated kinase (AMPK)-p38 pathway, leading to cyclin D1 degradation, Rb dephosphorylation, and subsequent E2F1 inhibition. Our results thus connect OXPHOS uncoupling to the inhibition of an essential oncogenic pathway, supporting repositioning NTZ and other mitochondrial uncouplers for prostate cancer therapy.

Indexed as

E2F1 Transcription FactorMitochondriaProstatic NeoplasmsUncoupling AgentsAdenosine TriphosphateAMP-Activated Protein KinasesAnimalsCell Line, TumorCell ProliferationCyclin D1Gene Expression Regulation, NeoplasticHumansMaleNitro CompoundsOxidative PhosphorylationThiazolesAdenosine TriphosphateAMP-Activated Protein KinasesCyclin D1E2F1 protein, humanE2F1 Transcription FactornitazoxanideNitro CompoundsThiazolesUncoupling AgentsAMPKcyclin D1E2F1mitochondrial uncouplernitazoxanideoxidative phosphorylationp38prostate cancerSKP2tizoxanide

Identifiers

PMID39793570
PMCPMC11866447

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.