Evidence map›Paper›PMID 34625047›Full record

ArticleBMC cancer2021

Novel chemotherapeutic agent FX-9 activates NF-κB signaling and induces G1 phase arrest by activating CDKN1A in a human prostate cancer cell line.

F Weiner, J T Schille, D Koczan, X-F Wu, M Beller, C Junghanss, M Hewicker-Trautwein, H Murua Escobar, I Nolte

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

Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact, top 89% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. 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

9 authors at 3 institutions in 1 country.

F WeinerSmall Animal Clinic, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.
J T SchilleSmall Animal Clinic, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.
D KoczanCore Facility for Microarray Analysis, Institute for Immunology, University of Rostock, 18057, Rostock, Germany.
X-F WuLeibniz Institute for Catalysis, 18059, Rostock, Germany.
M BellerLeibniz Institute for Catalysis, 18059, Rostock, Germany.
C JunghanssDepartment of Medicine, Clinic III, Hematology, Oncology, Palliative Medicine, University of Rostock, 18057, Rostock, Germany.
M Hewicker-TrautweinDepartment of Pathology, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.
H Murua Escobar *Department of Medicine, Clinic III, Hematology, Oncology, Palliative Medicine, University of Rostock, 18057, Rostock, Germany.
I Nolte *Small Animal Clinic, University of Veterinary Medicine Hannover, 30559, Hannover, Germany. Ingo.Nolte@tiho-hannover.de.
University of Veterinary Medicine Hannover, Foundation · DEUniversity of Rostock · DELeibniz Institute for Catalysis · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe aminoisoquinoline FX-9 shows pro-apoptotic and antimitotic effects against lymphoblastic leukemia cells and prostate adenocarcinoma cells. In contrast, decreased cytotoxic effects against non-neoplastic blood cells, chondrocytes, and fibroblasts were observed. However, the actual FX-9 molecular mode of action is currently not fully understood.

methodsIn this study, microarray gene expression analysis comparing FX-9 exposed and unexposed prostate cancer cells (PC-3 representing castration-resistant prostate cancer), followed by pathway analysis and gene annotation to functional processes were performed. Immunocytochemistry staining was performed with selected targets.

resultsExpression analysis revealed 0.83% of 21,448 differential expressed genes (DEGs) after 6-h exposure of FX-9 and 0.68% DEGs after 12-h exposure thereof. Functional annotation showed that FX-9 primarily caused an activation of inflammatory response by non-canonical nuclear factor-kappa B (NF-κB) signaling. The 6-h samples showed activation of the cell cycle inhibitor CDKN1A which might be involved in the secondary response in 12-h samples. This secondary response predominantly consisted of cell cycle-related changes, with further activation of CDKN1A and inhibition of the transcription factor E2F1, including downstream target genes, resulting in G1-phase arrest. Matching our previous observations on cellular level senescence signaling pathways were also found enriched. To verify these results immunocytochemical staining of p21 Waf1/Cip1 (CDKN1A), E2F1 (E2F1), PAI-1 (SERPNE1), and NFkB2/NFkB p 100 (NFKB2) was performed. Increased expression of p21 Waf1/Cip1 and NFkB2/NFkB p 100 after 24-h exposure to FX-9 was shown. E2F1 and PAI-1 showed no increased expression.

conclusionsFX-9 induced G1-phase arrest of PC-3 cells through activation of the cell cycle inhibitor CDKN1A, which was initiated by an inflammatory response of noncanonical NF-κB signaling.

Indexed as

Antineoplastic AgentsCyclin-Dependent Kinase Inhibitor p21E2F1 Transcription FactorG1 Phase Cell Cycle CheckpointsGene ExpressionGene Expression ProfilingHumansIsoquinolinesMaleMiddle AgedNF-kappa BPC-3 CellsPlasminogen Activator Inhibitor 1Prostatic Neoplasms, Castration-ResistantS Phase Cell Cycle CheckpointsTime Factors3-(p-tolyl)isoquinolin-1-amineAntineoplastic AgentsCDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21E2F1 protein, humanE2F1 Transcription FactorIsoquinolinesNF-kappa BPlasminogen Activator Inhibitor 1SERPINE1 protein, humanAntimitotic agentG1-phase arrestIsoquinolinamine FX-9Microarray analysisNF-κB signalingProstate cancer

Identifiers

PMID34625047
PMCPMC8501574
OpenAlexW3204392012

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.