J Cancer Prev.
2017 Mar;22(1):16-21. 10.15430/JCP.2017.22.1.16.
Ursodeoxycholic Acid Induces Death Receptor-mediated Apoptosis in Prostate Cancer Cells
- Affiliations
-
- 1Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea. lwshmo@gshp.gsnu.ac.kr gnuhjjm@gnu.ac.kr
- 2Department of Emergency Medicine, Gyeongsang National University School of Medicine, Jinju, Korea.
- 3Department of Pharmacology, Gyeongsang National University School of Medicine, Jinju, Korea.
- 4Institute of Health Sciences, Gyeongsang National University, Jinju, Korea. lwshmo@gshp.gsnu.ac.kr gnuhjjm@gnu.ac.kr
- 5School of Veterinary Medicine, Gyeongsang National University, Jinju, Korea.
- 6Research Institute of Life Science, Gyeongsang National University, Jinju, Korea.
- 7Division of Applied Life Science (BK 21 Program), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, Korea.
- 8Department of Chemistry, College of Natural Sciences, Gyeongsang National University, Jinju, Korea.
- 9Department of Surgery, Gyeongsang National University School of Medicine, Jinju, Korea.
- 10Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, Korea.
- 11Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University, Busan, Korea.
- 12Department of Neurosurgery, Gyeongsang National University School of Medicine, Jinju, Korea.
- KMID: 2375544
- DOI: http://doi.org/10.15430/JCP.2017.22.1.16
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.
Keyword
MeSH Terms
-
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*
Bile Acids and Salts
Caspase 8
Cytochromes c
DNA
Receptors, TNF-Related Apoptosis-Inducing Ligand
Ursodeoxycholic Acid
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