Ursodeoxycholic Acid Induces Death Receptor-mediated Apoptosis in Prostate Cancer Cells.
10.15430/JCP.2017.22.1.16
- Author:
Won Sup LEE
1
;
Ji Hyun JUNG
;
Radha PANCHANATHAN
;
Jeong Won YUN
;
Dong Hoon KIM
;
Hye Jung KIM
;
Gon Sup KIM
;
Chung Ho RYU
;
Sung Chul SHIN
;
Soon Chan HONG
;
Yung Hyun CHOI
;
Jin Myung JUNG
Author Information
1. Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea. lwshmo@gshp.gsnu.ac.kr gnuhjjm@gnu.ac.kr
- Publication Type:Original Article
- Keywords:
Ursodeoxycholic acid;
DU145;
Apoptosis;
Tumor necrosis factor-related apoptosis-inducing ligand;
Prostate cancer
- MeSH:
Apoptosis*;
Bile Acids and Salts;
Blister;
Blotting, Western;
Caspase 8;
Cell Death;
Cell Survival;
Cytochromes c;
Cytoplasm;
DNA;
Humans;
Necrosis;
Prostate*;
Prostatic Neoplasms*;
Receptors, TNF-Related Apoptosis-Inducing Ligand;
Ursodeoxycholic Acid*
- From:Journal of Cancer Prevention
2017;22(1):16-21
- CountryRepublic of Korea
- Language:English
-
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 cytochrome c and 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.
