Evidence map›Paper›PMID 38200580›Full record

ArticleJournal of experimental & clinical cancer research : CR2024

Marinopyrrole derivative MP1 as a novel anti-cancer agent in group 3 MYC-amplified Medulloblastoma.

Don W Coulter, Yashpal S Chhonker, Devendra Kumar, Varun Kesherwani, Wafaa N Aldhafiri, Erin M McIntyre, Gracey Alexander, Sutapa Ray, Shantaram S Joshi, Rongshi Li and 2 more

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

Article in Journal of experimental & clinical cancer research : CR, 2024. 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
2.2field-weighted citation impact, top 14% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  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

12 authors at 2 institutions in 1 country.

Don W CoulterDepartment of Pediatrics, Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Yashpal S ChhonkerDepartment of Pharmacy Practice & Science, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Devendra KumarDepartment of Pediatrics, Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Varun KesherwaniChild Health Research Institute, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Wafaa N AldhafiriDepartment of Pharmacy Practice & Science, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Erin M McIntyreDepartment of Pediatrics, Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Gracey AlexanderDepartment of Pediatrics, Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Sutapa RayDepartment of Pediatrics, Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Shantaram S JoshiDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Rongshi LiDepartment of Pharmacy Practice & Science, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Daryl J MurryDepartment of Pharmacy Practice & Science, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Nagendra K ChaturvediDepartment of Pediatrics, Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE, 68198, USA. nchaturvedi@unmc.edu.ORCID http://orcid.org/0000-0001-7037-898X
University of Nebraska Medical Center · USNebraska Medical Center · US

Funding

The State of Nebraska CHRI-PCRG Grant Funds (LB905)The Team Jack Foundation Power 5 Grant
6 · The paper itself

Abstract

backgroundMedulloblastoma (MB) patients with MYC oncogene amplification or overexpression exhibit extremely poor prognoses and therapy resistance. However, MYC itself has been one of the most challenging targets for cancer treatment. Here, we identify a novel marinopyrrole natural derivative, MP1, that shows desirable anti-MYC and anti-cancer activities in MB.

methodsIn this study, using MYC-amplified (Group 3) and non-MYC amplified MB cell lines in vitro and in vivo, we evaluated anti-cancer efficacies and molecular mechanism(s) of MP1.

resultsMP1 significantly suppressed MB cell growth and sphere counts and induced G2 cell cycle arrest and apoptosis in a MYC-dependent manner. Mechanistically, MP1 strongly downregulated the expression of MYC protein. Our results with RNA-seq revealed that MP1 significantly modulated global gene expression and inhibited MYC-associated transcriptional targets including translation/mTOR targets. In addition, MP1 inhibited MYC-target metabolism, leading to declined energy levels. The combination of MP1 with an FDA-approved mTOR inhibitor temsirolimus synergistically inhibited MB cell growth/survival by downregulating the expression of MYC and mTOR signaling components. Our results further showed that as single agents, both MP1 and temsirolimus, were able to significantly inhibit tumor growth and MYC expression in subcutaneously or orthotopically MYC-amplified MB bearing mice. In combination, there were further anti-MB effects on the tumor growth and MYC expression in mice.

conclusionThese preclinical findings highlight the promise of marinopyrrole MP1 as a novel MYC inhibition approach for MYC-amplified MB.

Indexed as

Cerebellar NeoplasmsMedulloblastomaAnimalsG2 Phase Cell Cycle CheckpointsHumansMiceSirolimusTOR Serine-Threonine KinasesSirolimustemsirolimusTOR Serine-Threonine KinasesMarinopyrrolesMedulloblastomaMetabolismMP1mTOR/translationMYC

Identifiers

PMID38200580
PMCPMC10782703
OpenAlexW4390742931

What Socratic 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 Socratic graph.