Ursodeoxycholic Acid Induces Death Receptor-mediated Apoptosis in Prostate Cancer Cells
Won Sup Lee1, Ji Hyun Jung1, Radha Panchanathan1
1Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea; Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
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.
Insights
Ursodeoxycholic acid (UDCA) effectively inhibits prostate cancer cell growth by triggering apoptosis through both extrinsic and intrinsic pathways. This bile acid shows promise as a novel anti-cancer therapeutic agent.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Bile acids possess known anti-cancer properties in specific cancer types.
- Ursodeoxycholic acid (UDCA) is a secondary bile acid with potential therapeutic applications.
Purpose of the Study:
- To investigate the anti-cancer activity of UDCA against human DU145 prostate cancer cells.
- To elucidate the molecular mechanisms underlying UDCA-induced apoptosis in prostate cancer.
Main Methods:
- Cell viability assessed using MTT assay.
- Apoptosis induction evaluated via flow cytometry.
- Expression of apoptosis-related proteins analyzed by Western blotting.
Main Results:
- UDCA significantly inhibited DU145 cell growth in a dose-dependent manner.
- UDCA induced apoptosis via both extrinsic (caspase 8, DR4, DR5, TRAIL) and intrinsic (Bax, cytochrome c, Bcl-xL) pathways.
- UDCA treatment led to cellular shrinkage and sub-G1 DNA accumulation.
Conclusions:
- UDCA effectively induces apoptosis in DU145 prostate cancer cells through dual extrinsic and intrinsic pathways.
- UDCA demonstrates potential as a promising anti-cancer agent for prostate cancer treatment.
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