title: 3-(2-Bromoethyl)-indole inhibits the growth of cancer cells and NF-κB activation.
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.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL, USA.
authors.forename: Khalda
authors.initials: K
authors.lastname: Fadlalla
authors.affiliation: Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: Ramy
authors.initials: R
authors.lastname: Elgendy
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL, USA.
authors.forename: Ebony
authors.initials: E
authors.lastname: Gilbreath
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
authors.forename: Satyanarayana R
authors.initials: SR
authors.lastname: Pondugula
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL, USA.
authors.forename: Teshome
authors.initials: T
authors.lastname: Yehualaeshet
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mansour
authors.affiliation: Department of Natural Sciences, Elizabeth City State University, Elizabeth City, NC, USA.
authors.forename: Tesfaye
authors.initials: T
authors.lastname: Serbessa
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Upender
authors.initials: U
authors.lastname: Manne
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL, USA.
authors.forename: Temesgen
authors.initials: T
authors.lastname: Samuel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C000606129:3-(2-bromoethyl)indole; D000970:Antineoplastic Agents; D007211:Indoles; D016328:NF-kappa B