Enhancement of Radiation Sensitivity in Lung Cancer Cells by a Novel Small Molecule Inhibitor That Targets the β-Catenin/Tcf4 Interaction

  • PLoS One. 2016 Mar 25;11(3):e0152407. doi: 10.1371/journal.pone.0152407.
Qinghao Zhang  1  2 ,  Mei Gao  1  2 ,  Guifen Luo  1  2 ,  Xiaofeng Han  1  2 ,  Wenjing Bao  1  2  3 ,  Yanyan Cheng  1  2  3 ,  Wang Tian  1  2 ,  Maocai Yan  4 ,  Guanlin Yang  3 ,  Jing An  1  2  5
Affiliations
  • 1. Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.
  • 2. SUNY Upstate Cancer Research Institute, State University of New York, Upstate Medical University, Syracuse, New York, United States of America.
  • 3. Department of Medicine, Liaoning University of Chinese Traditional Medicine, No. 33 Beiling Street, Huanggu District, Shenyang, China.
  • 4. Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, United States of America.
  • 5. Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
PMID: 27014877 DOI: 10.1371/journal.pone.0152407
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.

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