title: Smoothened inhibition leads to decreased proliferation and induces apoptosis in esophageal adenocarcinoma cells.
abstract: The Hedgehog (Hh) pathway is known to be active in Barrett's carcinogenesis. Therefore, we evaluated the efficacy and underlying mechanisms of inhibition of cancer cell growth by the smoothened (Smo) antagonist BMS-833923 in esophageal adenocarcinoma (EAC) cell lines. Cell proliferation and apoptosis were evaluated by flow cytometry, Western blotting, immunofluorescence, and quantitative reverse transcription polymerase chain reactions. Results showed that the Smo antagonist led to reduced Hh pathway activity, resulting in decreased cell proliferation and induction of apoptosis via the intrinsic pathway in the esophageal cancer cells. In conclusion, the Smo antagonist may have application as an EAC chemotherapeutic agent.
authors.affiliation: Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, Pennsylvania 15224, USA.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Zaidi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komatsu
authors.forename: Lori A
authors.initials: LA
authors.lastname: Kelly
authors.forename: Usha
authors.initials: U
authors.lastname: Malhotra
authors.forename: Christina
authors.initials: C
authors.lastname: Rotoloni
authors.forename: Juliann E
authors.initials: JE
authors.lastname: Kosovec
authors.forename: Haris
authors.initials: H
authors.lastname: Zahoor
authors.forename: Rory
authors.initials: R
authors.lastname: Makielski
authors.forename: Astha
authors.initials: A
authors.lastname: Bhatt
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Hoppo
authors.forename: Blair A
authors.initials: BA
authors.lastname: Jobe
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D000072086:Smoothened Receptor
chemical_list: D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor