Benzimidazoles Diminish ERE Transcriptional Activity and Cell Growth in Breast Cancer Cells.

Funding Source

National Science Foundation, National Institutes of Health, National Institutes of General Medical Sciences

Grant Number

0714553, 5P20MD000215-05, 8G12MD007595-04, 1SC2GM099599-01A1


College of Pharmacy

Document Type


Publication Date



Estrogen receptors (ERα and ERβ) are members of the nuclear receptor superfamily. They regulate the transcription of estrogen-responsive genes and mediate numerous estrogen related diseases (i.e., fertility, osteoporosis, cancer, etc.). As such, ERs are potentially useful targets for developing therapies and diagnostic tools for hormonally responsive human breast cancers. In this work, two benzimidazole-based sulfonamides originally designed to reduce proliferation in prostate cancer, have been evaluated for their ability to modulate growth in estrogen dependent and independent cell lines (MCF-7 and MDA-MB 231) using cell viability assays. The molecules reduced growth in MCF-7 cells, but differed in their impact on the growth of MDA-MB 231 cells. Although both molecules reduced estrogen response element (ERE) transcriptional activity in a dose dependent manner, the contrasting activity in the MDA-MB-231 cells seems to suggest that the molecules may act through alternate ER-mediated pathways. Further, the methyl analog showed modest selectivity for the ERβ receptor in an ER gene expression array panel, while the naphthyl analog did not significantly alter gene expression. The molecules were docked in the ligand binding domains of the ERα-Antagonist and ERβ-Agonist crystal structures to evaluate the potential of the molecules to interact with the receptors. The computational analysis complimented the results obtained in the assay of transcriptional activity and gene expression suggesting that the molecules upregulate ERβ activity while down regulating that of ERα.


DOI: 10.1016/j.bbrc.2014.06.130

PubMed ID: 24997336

Funding text

This publication was made possible in part by funding from the Louisiana Cancer Research Consortium, NIH- National Institute on Minority Health and Health Disparities RCMI Grant #8G12MD007595-04 and RIMI Grant #5P20MD000215-05 , NIH- National Institute of General Medical Sciences SCORE Grant #1SC2GM099599-01A1 , and the National Science Foundation Historically Black Colleges and Universities Undergraduate Program Grant #0714553 . All funding agencies are located in the United States. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the Louisiana Cancer Research Consortium, National Institutes of Health, or the National Science Foundation.