Evidence map›Paper›PMID 33196708›Full record

ArticleOncotarget2020

Targeting breast cancer metabolism with a novel inhibitor of mitochondrial ATP synthesis.

Myoung Sook Kim, Ramkishore Gernapudi, Yessenia Cedeño Cedeño, Brian M Polster, Ramon Martinez, Paul Shapiro, Santosh Kesari, Elmar Nurmemmedov, Antonino Passaniti

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.9field-weighted citation impact, top 31% 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

15 citing papers in PubMed, 19 citations in OpenAlex.

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  7. YBX1-interacting small RNAs andJournal of bone oncology · 2023
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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

9 authors at 4 institutions in 1 country.

Myoung Sook KimDepartment of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
Ramkishore GernapudiDepartment of Biochemistry & Molecular Biology and Program in Molecular Medicine, Baltimore, MD, USA.
Yessenia Cedeño CedeñoThe Marlene & Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Brian M PolsterDepartment of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Ramon MartinezDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA.
Paul ShapiroDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA.
Santosh KesariJohn Wayne Cancer Institute and Pacific Neuroscience Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.
Elmar NurmemmedovJohn Wayne Cancer Institute and Pacific Neuroscience Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.
Antonino PassanitiDepartment of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterSaint John's Health Center · USUniversity of Maryland, Baltimore · USVeterans Health Administration · US

Funding

EXPAND PARTICIPATION BY MINORITIES IN BIOMEDICAL SCIENCER25GM055036 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE COUNTY · PI SUMMERS, MICHAEL FINLEY · 1996 to 2021
$16.9M
Transcriptional regulation of tumor growthI01BX002205 · VA · BALTIMORE VA MEDICAL CENTER · PI PASSANITI, ANTONINO · 2014 to 2017
–
Mitochondrial metabolism as a target of breast cancer therapyI01BX004904 · VA · BALTIMORE VA MEDICAL CENTER · PI PASSANITI, ANTONINO · 2020 to 2024
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BLRD VA I01 BX002205BLRD VA I01 BX004904NIGMS NIH HHS R25 GM055036
6 · The paper itself

Abstract

Inhibitors of mitochondrial respiration and ATP synthesis may promote the selective killing of respiration-competent cancer cells that are critical for tumor progression. We previously reported that CADD522, a small molecule inhibitor of the RUNX2 transcription factor, has potential for breast cancer treatment. In the current study, we show that CADD522 inhibits mitochondrial oxidative phosphorylation by decreasing the mitochondrial oxygen consumption rate (OCR) and ATP production in human breast cancer cells in a RUNX2-independent manner. The enzyme activity of mitochondrial ATP synthase was inhibited by CADD522 treatment. Importantly, results from cellular thermal shift assays that detect drug-induced protein stabilization revealed that CADD522 interacts with both α and β subunits of the F1-ATP synthase complex. Differential scanning fluorimetry also demonstrated interaction of α subunits of the F1-ATP synthase to CADD522. These results suggest that CADD522 might target the enzymatic F1 subunits in the ATP synthase complex. CADD522 increased the levels of intracellular reactive oxygen species (ROS), which was prevented by MitoQ, a mitochondria-targeted antioxidant, suggesting that cancer cells exposed to CADD522 may elevate ROS from mitochondria. CADD522-increased mitochondrial ROS levels were enhanced by exogenously added pro-oxidants such as hydrogen peroxide or

Indexed as

ATP synthesismitochondrial ATP synthaseoxygen consumption ratereactive oxygen species

Identifiers

PMID33196708
PMCPMC7597410
OpenAlexW3094851652

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.