Evidence map›Paper›PMID 29531225›Full record

ArticleCell death & disease2018

Paraoxonase 2 overexpression inhibits tumor development in a mouse model of ovarian cancer.

Asokan Devarajan, Feng Su, Victor Grijalva, Meghna Yalamanchi, Ashna Yalamanchi, Feng Gao, Hannah Trost, Josephine Nwokedi, Gina Farias-Eisner, Robin Farias-Eisner and 2 more

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

Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.4field-weighted citation impact, top 13% 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

23 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Paraoxonase 2 as a target for aging-related diseases.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026
    Review
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  6. Article
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  8. Article
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  11. Review
  12. Article
  13. Oncoimmunology · 2022
    Article
  14. Article
  15. Article
  16. Review
  17. Human Paraoxonase-2 (PON2): Protein Functions and Modulation.Antioxidants (Basel, Switzerland) · 2021
    Review
  18. Review
  19. Article
  20. 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

12 authors at 2 institutions in 2 countries.

Asokan DevarajanDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1736, USA. adevarajan@mednet.ucla.edu.
Feng SuDepartment of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1736, USA.
Victor GrijalvaDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1736, USA.
Meghna YalamanchiDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1736, USA.
Ashna YalamanchiDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1736, USA.
Feng GaoDepartment of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1736, USA.
Hannah TrostDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1736, USA.
Josephine NwokediDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1736, USA.
Gina Farias-EisnerDepartment of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1736, USA.
Robin Farias-EisnerDepartment of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1736, USA.
Alan M FogelmanDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1736, USA.
Srinivasa T ReddyDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-1736, USA. sreddy@mednet.ucla.edu.
University of California, Los Angeles · USInner Mongolia Medical University · CN

Funding

ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2M
The role of PON2 and PON3 proteins in AtherosclerosisR01HL071776 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REDDY, SRINIVASA T. · 2003 to 2017
$4.8M
NHLBI NIH HHS P01 HL030568NHLBI NIH HHS R01 HL071776
6 · The paper itself

Abstract

Ovarian cancer (OC) is most lethal malignancy among all gynecological cancer. Large bodies of evidences suggest that mitochondrial-derived ROS play a critical role in the development and progression of OC. Paraoxonase 2 (PON2) is a membrane-associated lactonase with anti-oxidant properties. PON2 deficiency aggravates mitochondrial ROS formation, systemic inflammation, and atherosclerosis. The role of PON2 in cancer development remains unknown. In this report, in human, we identified that PON2 expression is higher in early stages (but not in late stages) of OC when compared to normal tissue. Using a mouse xenograft model of OC, we demonstrate that overexpression of PON2 prevents tumor formation. Mechanistically, PON2 decreases OC cell proliferation by inhibiting insulin like growth factor-1 (IGF-1) expression and signaling. Intriguingly, PON2 reduces c-Jun-mediated transcriptional activation of IGF-1 gene by decreasing mitochondrial superoxide generation. In addition, PON2 impairs insulin like growth factor-1 receptor (IGF-1R) signaling in OC cells by altering cholesterol homeostasis, which resulted in reduced caveolin-1/IGF-1R interaction and IGF-1R phosphorylation. Taken together, we report for the first time that PON2 acts as a tumor suppressor in the early stage of OC by reducing IGF-1 production and its signaling, indicating PON2 activation might be a fruitful strategy to inhibit early stage ovarian tumor.

Indexed as

AnimalsAryldialkylphosphataseCell Line, TumorDisease Models, AnimalFemaleHeterograftsHumansInsulin-Like Growth Factor IMiceMice, Inbred C57BLMitochondriaNeoplasm StagingOvarian NeoplasmsOxidative StressReactive Oxygen SpeciesReceptor, IGF Type 1AryldialkylphosphataseInsulin-Like Growth Factor IPON2 protein, humanReactive Oxygen SpeciesReceptor, IGF Type 1

Identifiers

PMID29531225
PMCPMC5847560
OpenAlexW2790911536

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.