Evidence map›Paper›PMID 40157458›Full record

ArticleBiochemical pharmacology2025

Suppression of global protein synthesis and hepatocellular carcinoma cell growth by Benzimidazoisoquinoline, 4,11-Dichloro-BBQ.

Lo-Wei Lin, Hyo Sang Jang, Zifeng Song, Arpa Ebrahimi, Jun Yang, Bach D Nguyen, Edmond F O'Donnell, David A Hendrix, Claudia S Maier, Siva K Kolluri

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

10 authors.

Lo-Wei LinCancer Research Laboratory, Department of Environmental & Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA.
Hyo Sang JangCancer Research Laboratory, Department of Environmental & Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA.
Zifeng SongDepartment of Chemistry, Oregon State University, Corvallis, OR 97331, USA.
Arpa EbrahimiDepartment of Chemistry, Oregon State University, Corvallis, OR 97331, USA.
Jun YangDepartment of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
Bach D NguyenCancer Research Laboratory, Department of Environmental & Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA.
Edmond F O'DonnellCancer Research Laboratory, Department of Environmental & Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA.
David A HendrixDepartment of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA; School of Electrical Engineering and Computer Science, Oregon State University, Corvallis, OR 97331, USA.
Claudia S MaierDepartment of Chemistry, Oregon State University, Corvallis, OR 97331, USA.
Siva K KolluriCancer Research Laboratory, Department of Environmental & Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA. Electronic address: siva.kolluri@oregonstate.edu.

Funding

MODE OF ACTION OF ENVIRONMENTAL TOXICANTST32ES007060 · NIEHS · OREGON STATE UNIVERSITY · PI Jamie DeWitt, Siva Kumar Kolluri · 1985 to 2026
$11.6M
Zebrafish Biomedical Research Facility CoreP30ES030287 · NIEHS · OREGON STATE UNIVERSITY · PI Jamie DeWitt · 2020 to 2026
$9.8M
Orbitrap Elite with ETDS10OD020111 · OD · OREGON STATE UNIVERSITY · PI MAIER, CLAUDIA S · 2015 to 2015
$600k
Aryl Hydrocarbon Receptor Modulators for the Treatment of Hepatocellular CarcinomR21ES019000 · NIEHS · OREGON STATE UNIVERSITY · PI KOLLURI, SIVA KUMAR · 2011 to 2012
$402k
NIEHS NIH HHS P30 ES030287NIEHS NIH HHS R21 ES019000NIEHS NIH HHS T32 ES007060NIH HHS S10 OD020111
6 · The paper itself

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor best known for mediating biological responses to a wide range of xenobiotics, such as dioxins and polycyclic aromatic hydrocarbons. Recently, AhR has emerged as an important player in cancer biology, with the potential for therapeutic applications through targeted modulation of its activity in specific cancer types. In this study, we report that 4,11-dichloro-BBQ (DiCl-BBQ), a benzimidazoisoquinoline, exhibits AhR-mediated antiproliferative activity in HepG2 hepatocellular carcinoma cells. DiCl-BBQ was found to decrease cell growth at nanomolar concentrations, and this antiproliferative effect persisted even after the compound's removal. Using inducible shRNA expression system, we demonstrated that the inhibitory effect of DiCl-BBQ was significantly reduced following AhR knockdown. Flow cytometric analysis revealed that DiCl-BBQ halted cell division and induced G1 cell cycle arrest in an AhR-dependent manner. Proteomic profiling identified the top four enriched pathways following DiCl-BBQ exposure: metabolism of RNA, translation, ribonucleoprotein complex biogenesis, and carboxylic acid metabolic processes. Notably, DiCl-BBQ caused a dramatic downregulation of translation-associated proteins, with this response diminished in AhR-depleted cells. Consistently, global protein synthesis was significantly repressed in DiCl-BBQ-treated cells. Together, these results indicate that DiCl-BBQ effectively inhibits HepG2 cells growth by inducing G1 cell cycle arrest and downregulating the protein translation machinery in an AhR-dependent manner.

Indexed as

Antineoplastic AgentsCarcinoma, HepatocellularCell ProliferationIsoquinolinesLiver NeoplasmsProtein BiosynthesisHep G2 CellsHumansReceptors, Aryl HydrocarbonAntineoplastic AgentsIsoquinolinesReceptors, Aryl Hydrocarbon4,11-dichloro-BBQAntiproliferative effectAryl hydrocarbon receptorG1 cell cycle arrestHepG2 hepatocellular carcinoma cellsInhibition of protein translation

Identifiers

PMID40157458
PMCPMC12285656

What OpenQuestion holds

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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.