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| Content Provider | PubMed Central |
|---|---|
| Author | Shin, Eun Ah Sohn, Eun Jung Won, Gunho Choi, Jeong-un Jeong, Myongsuk Kim, Bonglee Kim, Min-jeong Kim, Sung-hoon |
| Copyright Year | 2014 |
| Abstract | Though tumor necrosis factor related apoptosis inducing ligand (TRAIL) has been used as a potent anticancer agent, TRAIL resistance is a hot-issue in cancer therapy. We investigated the antitumor mechanism of Tanshinone I to sensitize prostate cancer cells to TRAIL. Comibination of Tanshinone I and TRAIL exerted synergistic cytotoxicity, increased cleaved PARP, sub G1 population, the number of TUNELpositive cells, activated caspase 8, 9 and ROS production in PC-3 and DU145 cells. Of note, combination of Tanshinone I and TRAIL enhanced the protein expression of death receptor 5 (DR5) and attenuated anti-apoptotic proteins. RT-PCR and RT-qPCR analyses confirmed that co-treatment of Tanshinone I and TRAIL up-regulated DR5 and microRNA 135a-3p at mRNA level or activity of DR5 promoter and attenuated phosphorylation of extracellular signal regulated kinases in PC-3. Conversely, the silencing of DR5 blocked the increased cytotoxicity, sub G1 population and PARP cleavages induced by co-treatment of Tanshinone I and TRAIL. Interestingly, miR135a-3p mimic enhanced DR5 at mRNA, increased PARP cleavage, Bax and the number of TUNEL positive cells in Tanshinone I and TRAIL cotreated PC-3. Overall, our findings suggest that Tanshinone I enhances TRAIL mediated apoptosis via upregulation of miR135a-3p mediated DR5 in prostate cancer cells as a potent TRAIL sensitizer. |
| Ending Page | 5636 |
| Starting Page | 5624 |
| File Format | |
| ISSN | 19492553 |
| e-ISSN | 19492553 |
| Journal | Oncotarget |
| Issue Number | 14 |
| Volume Number | 5 |
| Language | English |
| Publisher | Impact Journals LLC |
| Publisher Date | 2014-06-30 |
| Access Restriction | Open |
| Rights Holder | Impact Journals LLC |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology |
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