TitleInduction of Aryl Hydrocarbon Receptor-Mediated Cancer Cell-Selective Apoptosis in Triple-Negative Breast Cancer Cells by a High-Affinity Benzimidazoisoquinoline.
Publication TypeJournal Article
Year of Publication2023
AuthorsElson DJ, Nguyen BD, Bernales S, Chakravarty S, Jang HSang, Korjeff NA, Zhang Y, Wilferd SF, Castro DJ, Plaisier CL, Finlay D, Oshima RG, Kolluri SK
JournalACS Pharmacol Transl Sci
Date Published2023 Jul 14

Triple-negative breast cancer (TNBC) remains a disease with a paucity of targeted treatment opportunities. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is involved in a wide range of physiological processes, including the sensing of xenobiotics, immune function, development, and differentiation. Different small-molecule AhR ligands drive strikingly varied cellular and organismal responses. In certain cancers, AhR activation by select small molecules induces cell cycle arrest or apoptosis via activation of tumor-suppressive transcriptional programs. AhR is expressed in triple-negative breast cancers, presenting a tractable therapeutic opportunity. Here, we identify a novel ligand of the aryl hydrocarbon receptor that potently and selectively induces cell death in triple-negative breast cancer cells and TNBC stem cells via the AhR. Importantly, we found that this compound, Analog 523, exhibits minimal cytotoxicity against multiple normal human primary cells. Analog 523 represents a high-affinity AhR ligand with potential for future clinical translation as an anticancer agent.

Alternate JournalACS Pharmacol Transl Sci
PubMed ID37470014
PubMed Central IDPMC10353065