title: Combination of isoliquiritigenin and tumor necrosis factor-related apoptosis-inducing ligand induces apoptosis in colon cancer HT29 cells.
abstract: OBJECTIVE
  Isoliquiritigenin is a chalcone derivative with potential in cancer chemoprevention. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent, some cancer cells are resistant to TRAIL treatment. Current studies have tried to overcome TRAIL-resistant cancer cells. Here, we show for the first time that isoliquiritigenin overcomes TRAIL resistance in colon cancer HT29 cells.
  
  
  METHODS
  HT29 cells were treated with isoliquiritigenin and/or TRAIL, and apoptosis induction was detected by flow cytometry and fluorescence microscopy. Protein expression relating to the TRAIL pathway was analyzed by Western blotting.
  
  
  RESULTS
  A single treatment with isoliquiritigenin scarcely induced apoptosis in HT29 cells. Combined treatment with suboptimal concentrations of isoliquiritigenin and TRAIL markedly induced apoptosis, however. The effect was blocked by a pan-caspase inhibitor and a caspase-3, 8, 9, or 10 inhibitor, suggesting that the combination facilitates caspase-dependent apoptosis. Furthermore, the apoptosis induced by isoliquiritigenin and TRAIL was blocked by a dominant negative form of the TRAIL receptor. This result indicates that the combined effect is caused by specific interaction between TRAIL and its receptors. Isoliquiritigenin increased the amount of DR5 protein among TRAIL receptors. Isoliquiritigenin did not significantly increase levels of the Bcl-2 family proteins Bcl-2, Bcl-xL, and BAX.
  
  
  CONCLUSIONS
  Our results suggest that isoliquiritigenin has the potential to overcome resistance to TRAIL in cancer cells and its chemopreventive effects may depend on TRAIL function.
authors: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Tatsushi
authors: T
authors: Yoshida
authors: Mano
authors: M
authors: Horinaka
authors: Mami
authors: M
authors: Takara
authors: Mayuko
authors: M
authors: Tsuchihashi
authors: Nobuhiro
authors: N
authors: Mukai
authors: Miki
authors: M
authors: Wakada
authors: Toshiyuki
authors: T
authors: Sakai