title: Ursodeoxycholic Acid Induces Death Receptor-mediated Apoptosis in Prostate Cancer Cells.
abstract: BACKGROUND
  Bile acids have anti-cancer properties in a certain types of cancers. We determined anticancer activity and its underlying molecular mechanism of ursodeoxycholic acid (UDCA) in human DU145 prostate cancer cells.
  
  
  METHODS
  Cell viability was measured with an MTT assay. UDCA-induced apoptosis was determined with flow cytometric analysis. The expression levels of apoptosis-related signaling proteins were examined with Western blotting.
  
  
  RESULTS
  UDCA treatment significantly inhibited cell growth of DU145 in a dose-dependent manner. It induced cellular shrinkage and cytoplasmic blebs and accumulated the cells with sub-G1 DNA contents. Moreover, UDCA activated caspase 8, suggesting that UDCA-induced apoptosis is associated with extrinsic pathway. Consistent to this finding, UDCA increased the expressions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor, death receptor 4 (DR4) and death receptor 5 (DR5), and TRAIL augmented the UDCA-induced cell death in DU145 cells. In addition, UDCA also increased the expressions of Bax and cytochromecand decreased the expression of Bcl-xL in DU145 cells. This finding suggests that UDCA-induced apoptosis may be involved in intrinsic pathway.
  
  
  CONCLUSIONS
  UDCA induces apoptosis via extrinsic pathway as well as intrinsic pathway in DU145 prostate cancer cells. UDCA may be a promising anti-cancer agent against prostate cancer.
authors.affiliation: Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea; Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea; Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea; Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
authors.forename: Radha
authors.initials: R
authors.lastname: Panchanathan
authors.affiliation: Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea; Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Yun
authors.affiliation: Department of Emergency Medicine, Gyeongsang National University School of Medicine, Jinju, Korea; Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Gyeongsang National University School of Medicine, Jinju, Korea; Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: School of Veterinary Medicine, Gyeongsang National University, Jinju, Korea; Research Institute of Life Science, Gyeongsang National University, Jinju, Korea.
authors.forename: Gon Sup
authors.initials: GS
authors.lastname: Kim
authors.affiliation: Division of Applied Life Science (BK 21 Program), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, Korea.
authors.forename: Chung Ho
authors.initials: CH
authors.lastname: Ryu
authors.affiliation: Research Institute of Life Science, Gyeongsang National University, Jinju, Korea; Department of Chemistry, College of Natural Sciences, Gyeongsang National University, Jinju, Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Shin
authors.affiliation: Institute of Health Sciences, Gyeongsang National University, Jinju, Korea; Department of Surgery, Gyeongsang National University School of Medicine, Jinju, Korea.
authors.forename: Soon Chan
authors.initials: SC
authors.lastname: Hong
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, Korea; Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University, Busan, Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Institute of Health Sciences, Gyeongsang National University, Jinju, Korea; Department of Neurosurgery, Gyeongsang National University School of Medicine, Jinju, Korea.
authors.forename: Jin-Myung
authors.initials: JM
authors.lastname: Jung
keywords: Apoptosis; DU145; Prostate cancer; Tumor necrosis factor-related apoptosis-inducing ligand; Ursodeoxycholic acid