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KMID : 1140220170220010016
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대한암예방학회지
2017 Volume.22 No. 1 p.16 ~ p.21
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Ursodeoxycholic Acid Induces Death Receptor-mediated Apoptosis in Prostate Cancer Cells
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Lee Won-Sup
Jung Ji-Hyun
Panchanathan Radha
Yun Jeong-Won
Kim Dong-Hoon
Kim Hye-Jung
Kim Gon-Sup
Ryu Chung-Ho
Shin Sung-Chul
Hong Soon-Chan
Choi Yung-Hyun
Jung Jin-Myung
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Abstract
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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.
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KEYWORD
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Ursodeoxycholic acid, DU145, Apoptosis, Tumor necrosis factor-related apoptosis-inducing ligand, Prostate cancer
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