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AMP-activated protein kinase (AMPK) as a potential therapeutic target independent of PI3K/Akt signaling in prostate cancer
| Content Provider | Semantic Scholar |
|---|---|
| Author | Choudhury, Yashmin Yang, Zichu Ahmad, Imran Nixon, Colin Salt, Ian P. Leung, Hing Y. |
| Copyright Year | 2014 |
| Abstract | Depletion of cellular energy activates the AMP-activated kinase (AMPK) to favor energy-producing catabolic processes during tumorigenesis. Using a panel of in vitro cell lines and resected tumors, we investigated the therapeutic value of manipulating AMPK in prostate cancer (PC). Phospho-AMPK expression was significantly elevated in human PC cells and clinical PC samples. In clinical PC, we observed a trend for increasing phospho-AMPK with increasing Gleason sum score; Phospho-AMPK expression was associated with phospho-ACC (p=0.0023). Using the paired PC3 and PC3M cells to model progressive androgen-independent PC, treatment with either 5-aminoimidazole-4-carboxamide riboside (AICAR) or A-769662 suppressed proliferation, migration and invasion in both cell lines, and down-regulated mTOR and P70S6Ki levels regardless of the Akt status. Involvement of AMPK was confirmed by Compound C (AMPK inhibitor) and siRNA-mediated AMPK silencing. Despite similar functional responses in PC3 and PC3M cells, AMPK activation resulted in sustained phospho-Akt activation in PC3M cells, but not in PC3 cells. This prompted the addition of the PI3K inhibitor LY-294002 to AICAR treatment of PC3M cells in a proliferation assay. Interestingly, we found no synergistic effects upon combined treatment. Collectively, these findings support AMPK as a potential therapeutic target independent of PI3K/Akt signalling. |
| Starting Page | 446 |
| Ending Page | 456 |
| Page Count | 11 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://eprints.gla.ac.uk/105176/1/105176.pdf |
| Alternate Webpage(s) | http://www.impactjournals.com/oncoscience/files/papers/1/49/49.pdf |
| PubMed reference number | 25594043v1 |
| Volume Number | 1 |
| Journal | Oncoscience |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 1-Phosphatidylinositol 3-Kinase A 769662 AICA ribonucleotide AMP-Activated Protein Kinases Androgens Carcinogenesis Cultured Cell Line LY 294002 Prostatic Neoplasms Proto-Oncogene Proteins c-akt acadesine biological signaling riboside |
| Content Type | Text |
| Resource Type | Article |
