Ursodeoxycholic Acid Induces Death Receptor-mediated Apoptosis in Prostate Cancer Cells.

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Ursodeoxycholic Acid Induces Death Receptor-mediated Apoptosis in Prostate Cancer Cells.

J Cancer Prev. 2017 Mar;22(1):16-21

Authors: Lee WS, Jung JH, Panchanathan R, Yun JW, Kim DH, Kim HJ, Kim GS, Ryu CH, Shin SC, Hong SC, Choi YH, Jung JM

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.

PMID: 28382282 [PubMed - in process]

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