Evidence map›Paper›PMID 38605607›Full record

ArticleMolecular oncology2024

Manzamine A reduces androgen receptor transcription and synthesis by blocking E2F8-DNA interactions and effectively inhibits prostate tumor growth in mice.

Dev Karan, Seema Dubey, Sumedha Gunewardena, Kenneth A Iczkowski, Manohar Singh, Pengyuan Liu, Angelo Poletti, Yeun-Mun Choo, Hui-Zi Chen, Mark T Hamann

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 21% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. 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

10 authors at 5 institutions in 3 countries.

Dev KaranDepartment of Pathology, and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.ORCID 0000-0002-0905-0886
Seema DubeyDepartment of Pathology, and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Sumedha GunewardenaDepartment of Cell Biology and Physiology, University of Kansas Medical Center, KS, USA.
Kenneth A IczkowskiDepartment of Pathology, and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Manohar SinghDepartment of Pathology, and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Pengyuan LiuDepartment of Physiology and Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Angelo PolettiDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Italy.
Yeun-Mun ChooDepartment of Chemistry, University of Malaya, Kuala Lumpur, Malaysia.
Hui-Zi ChenDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Mark T HamannDepartment of Drug Discovery and Biomedical Sciences and Public Health, Colleges of Pharmacy and Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Medical College of Wisconsin · USMedical University of South Carolina · USUniversity of Kansas Medical Center · USUniversity of Malaya · MYUniversity of Milan · IT

Funding

Synthesis and Optimization of the Aleutianamine Class of AlkaloidsR01GM145845 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HAMANN, MARK T, TIUS, MARCUS ANTONIUS · 2022 to 2025
$2.4M
Natural Product HCV Drugs from Rare Plant-Microbe InteractionsR01AT007318 · NCCIH · UNIVERSITY OF MISSISSIPPI · PI HAMANN, MARK T · 2012 to 2016
$1.6M
Medicines for Malaria VentureNCCIH NIH HHS R01 AT007318NCCIH NIH HHS RO1AT007318NIGMS NIH HHS R01 GM145845
6 · The paper itself

Abstract

The androgen receptor (AR) is the main driver in the development of castration-resistant prostate cancer, where the emergence of AR splice variants leads to treatment-resistant disease. Through detailed molecular studies of the marine alkaloid manzamine A (MA), we identified transcription factor E2F8 as a previously unknown regulator of AR transcription that prevents AR synthesis in prostate cancer cells. MA significantly inhibited the growth of various prostate cancer cell lines and was highly effective in inhibiting xenograft tumor growth in mice without any pathophysiological perturbations in major organs. MA suppressed the full-length AR (AR-FL), its spliced variant AR-V7, and the AR-regulated prostate-specific antigen (PSA; also known as KLK3) and human kallikrein 2 (hK2; also known as KLK2) genes. RNA sequencing (RNA-seq) analysis and protein modeling studies revealed E2F8 interactions with DNA as a potential novel target of MA, suppressing AR transcription and its synthesis. This novel mechanism of blocking AR biogenesis via E2F8 may provide an opportunity to control therapy-resistant prostate cancer over the currently used AR antagonists designed to target different parts of the AR gene.

Indexed as

Prostatic NeoplasmsReceptors, AndrogenTranscription, GeneticAnimalsCell Line, TumorCell ProliferationDNAGene Expression Regulation, NeoplasticHumansMaleMiceMice, NudeXenograft Model Antitumor AssaysDNAReceptors, Androgenandrogen receptorE2F8manzamine Aprostate cancer

Identifiers

PMID38605607
PMCPMC11306517
OpenAlexW4394756972

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.