11-Cl-BBQ, a select modulator of AhR-regulated transcription, suppresses lung cancer cell growth via activation of p53 and p27Kip1

FEBS J. 2023 Apr;290(8):2064-2084. doi: 10.1111/febs.16683. Epub 2022 Dec 22.


Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and functions as a tumour suppressor in different cancer models. In the present study, we report detailed characterization of 11-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (11-Cl-BBQ) as a select modulator of AhR-regulated transcription (SMAhRT) with anti-cancer actions. Treatment of lung cancer cells with 11-Cl-BBQ induced potent and sustained AhR-dependent anti-proliferative effects by promoting G1 phase cell cycle arrest. Investigation of 11-Cl-BBQ-induced transcription in H460 cells with or without the AhR expression by RNA-sequencing revealed activation of p53 signalling. In addition, 11-Cl-BBQ suppressed multiple pathways involved in DNA replication and increased expression of cyclin-dependent kinase inhibitors, including p27Kip1 , in an AhR-dependent manner. CRISPR/Cas9 knockout of individual genes revealed the requirement for both p53 and p27Kip1 for the AhR-mediated anti-proliferative effects. Our results identify 11-Cl-BBQ as a potential lung cancer therapeutic, highlight the feasibility of targeting AhR and provide important mechanistic insights into AhR-mediated-anticancer actions.

Keywords: 11-Cl-BBQ; AhR; G1 phase cell cycle arrest; SA-β-gal; p27Kip1; p53.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Humans
  • Lung / metabolism
  • Lung Neoplasms* / genetics
  • RNA
  • Receptors, Aryl Hydrocarbon* / genetics
  • Receptors, Aryl Hydrocarbon* / metabolism
  • Tumor Suppressor Protein p53 / genetics


  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Receptors, Aryl Hydrocarbon
  • RNA
  • Tumor Suppressor Protein p53
  • 11-Cl-BBQ