title: Enhancement of Radiation Sensitivity in Lung Cancer Cells by a Novel Small Molecule Inhibitor That Targets the β-Catenin/Tcf4 Interaction.
abstract: Radiation therapy is an important treatment choice for unresectable advanced human lung cancers, and a critical adjuvant treatment for surgery. However, radiation as a lung cancer treatment remains far from satisfactory due to problems associated with radiation resistance in cancer cells and severe cytotoxicity to non-cancer cells, which arise at doses typically administered to patients. We have recently identified a promising novel inhibitor of β-catenin/Tcf4 interaction, named BC-23 (C21H14ClN3O4S), which acts as a potent cell death enhancer when used in combination with radiation. Sequential exposure of human p53-null non-small cell lung cancer (NSCLC) H1299 cells to low doses of x-ray radiation, followed 1 hour later by administration of minimally cytotoxic concentrations of BC-23, resulted in a highly synergistic induction of clonogenic cell death (combination index <1.0). Co-treatment with BC-23 at low concentrations effectively inhibits Wnt/β-catenin signaling and down-regulates c-Myc and cyclin D1 expression. S phase arrest and ROS generation are also involved in the enhancement of radiation effectiveness mediated by BC-23. BC-23 therefore represents a promising new class of radiation enhancer.
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.|SUNY Upstate Cancer Research Institute, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.
authors.forename: Qinghao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.|SUNY Upstate Cancer Research Institute, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.
authors.forename: Mei
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.|SUNY Upstate Cancer Research Institute, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.
authors.forename: Guifen
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.|SUNY Upstate Cancer Research Institute, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.|SUNY Upstate Cancer Research Institute, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.|Department of Medicine, Liaoning University of Chinese Traditional Medicine, No. 33 Beiling Street, Huanggu District, Shenyang, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Bao
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.|SUNY Upstate Cancer Research Institute, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.|Department of Medicine, Liaoning University of Chinese Traditional Medicine, No. 33 Beiling Street, Huanggu District, Shenyang, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.|SUNY Upstate Cancer Research Institute, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.
authors.forename: Wang
authors.initials: W
authors.lastname: Tian
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, United States of America.
authors.forename: Maocai
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Medicine, Liaoning University of Chinese Traditional Medicine, No. 33 Beiling Street, Huanggu District, Shenyang, China.
authors.forename: Guanlin
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.|SUNY Upstate Cancer Research Institute, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.|Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: An
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D001667:Binding, Competitive; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000628:therapy; D002453:Cell Cycle; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000166:cytology; D015376:Nimustine / Q000737:chemistry*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism*; D014965:X-Rays; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin; D015376:Nimustine; D019938:Cyclin D1; D008156:Luciferases