title: Parthenolide Sensitizes Human Colorectal Cancer Cells to Tumor Necrosis Factor-related Apoptosis-inducing Ligand through Mitochondrial and Caspase Dependent Pathway.
abstract: OBJECTIVE
  Combination therapy utilizing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in conjunction with other anticancer agents, is a promising strategy to overcome TRAIL resistance in malignant cells. Recently, parthenolide (PT) has proved to be a promising anticancer agent, and several studies have explored its use in combination therapy. Here, we investigated the molecular mechanisms by which PT sensitizes colorectal cancer (CRC) cells to TRAIL-induced apoptosis.
  
  
  METHODS
  HT-29 cells (TRAIL-resistant) were treated with PT and/or TRAIL for 24 hours. The inhibitory effect on proliferation was detected using the 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Annexin V staining, cell cycle analysis, and Hoechst 33258 staining were used to assess apoptotic cell death. Activation of an apoptotic pathway was confirmed by Western blot.
  
  
  RESULTS
  Treatment with TRAIL alone inhibited the proliferation of HCT 116 cells in a dose-dependent manner, whereas proliferation was not affected in HT-29 cells. Combination PT and TRAIL treatment significantly inhibited cell growth and induced apoptosis of HT-29 cells. We observed that the synergistic effect was associated with misregulation of B-cell lymphoma 2 (Bcl-2) family members, release of cytochrome C to the cytosol, activation of caspases, and increased levels of p53.
  
  
  CONCLUSIONS
  Combination therapy using PT and TRAIL might offer an effetive strategy to overcome TRAIL resistance in certain CRC cells.
authors.affiliation: Department of Internal Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea. ; Research Institute of Clinical Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Kieu Thi Thu
authors.initials: KT
authors.lastname: Trang
authors.affiliation: Department of Internal Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea. ; Research Institute of Clinical Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Se-Lim
authors.initials: SL
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Seung-Young
authors.initials: SY
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Chung-Hwan
authors.initials: CH
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Jin-Kyoung
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Jin-Chang
authors.initials: JC
authors.lastname: Moon
authors.affiliation: Department of Internal Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea. ; Research Institute of Clinical Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Soo-Teik
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea. ; Research Institute of Clinical Medicine, Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kim
keywords: Apoptosis; Colorectal neoplasm; Parthenolide; TRAIL; TRAIL resistance