3-(2-Bromoethyl)-indole inhibits the growth of cancer cells and NF-κB activation

Fadlalla,Khalda; Elgendy,Ramy; Gilbreath,Ebony; Pondugula,Satyanarayana R.; Yehualaeshet,Teshome; Mansour,Mahmoud; Serbessa,Tesfaye; Manne,Upender; Samuel,Temesgen

doi:10.3892/or.2015.3970

3-(2-Bromoethyl)-indole inhibits the growth of cancer cells and NF-κB activation

Authors:
- Khalda Fadlalla
- Ramy Elgendy
- Ebony Gilbreath
- Satyanarayana R. Pondugula
- Teshome Yehualaeshet
- Mahmoud Mansour
- Tesfaye Serbessa
- Upender Manne
- Temesgen Samuel
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Affiliations: Department of Pathobiology, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL, USA, Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt, Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA, Department of Natural Sciences, Elizabeth City State University, Elizabeth City, NC, USA, Department of Pathology and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
Published online on: May 11, 2015 https://doi.org/10.3892/or.2015.3970
Pages: 495-503

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Abstract

Indole-3-carbinol (I3C) and diindolylmethane (DIM), found in cruciferous vegetables, have chemopreventive and anticancer properties. In the present study, 14 substituted indoles were tested for activity against SW480 colon cancer cells. Among these, 3-(2-bromoethyl)-indole, named BEI-9, showed the greatest inhibition. The effects of BEI-9 on cancer cells were analyzed by MTS and CellTiter-Glo assays for effects on cell viability, by microscopy for phenotypic changes, by scratch wound assays for effects on migration, by flow cytometry for changes in the cell cycle, by immunoblotting for cyclin D and A to assess effects on cell cycle regulation, and by NF-κB reporter assays for effects on basal and drug-induced NF-κB activation. BEI-9 inhibited the growth of SW480 and HCT116 colon cancer cells at concentrations of 12.5 and 5 µM, respectively. BEI-9 also inhibited cell motility as determined with scratch wound assays, and reduced the levels of cyclin D1 and A. Furthermore, in reporter cells, BEI-9 (0.8 µM) inhibited basal and induced NF-κB activation and increased cell death when combined with the cytokine TNFα or the drug camptothecin (CPT), both of which activate NF-κB. Preliminary experiments to identify a safe dose range for immunodeficient mice showed that BEI-9, administered intraperitoneally, was tolerable at doses below 10 mg/kg. Thus, BEI-9 and other indole derivatives may be useful in chemoprevention or as chemosensitizers. Since NF-κB activation is implicated in carcinogenesis and in reducing sensitivity to anticancer drugs, BEI-9 should be investigated in combination with drugs such as CPT, which activate NF-κB.

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