Targeted AKT inhibition in prostate cancer cells and spheroids reduces aerobic glycolysis and generation of hyperpolarized [1-(13)C] lactate Journal Article
| Authors: | Tee, S. S.; Suster, I.; Truong, S.; Jeong, S.; Eskandari, R.; DiGialleonardo, V.; Alvarez, J. A.; Aldeborgh, H. N.; Keshari, K. R. |
| Article Title: | Targeted AKT inhibition in prostate cancer cells and spheroids reduces aerobic glycolysis and generation of hyperpolarized [1-(13)C] lactate |
| Abstract: | The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now in advanced clinical trials, and this study investigates the effect of MK2206, a non-ATP-competitive inhibitor, on the cellular metabolism of prostate cancer cells. We observed a reduction in cell motility and aerobic glycolysis in prostate cancer cells with treatment. These changes were not accompanied by a reduction in the ratio of high-energy phosphates or a change in total protein levels of enzymes and transporters involved in glycolysis. However, a decreased ratio of NADp/ NADH was observed, motivating the use of hyperpolarized magnetic resonance spectroscopy (HP-MRS) to detect treatment response. Spectroscopic experiments were performed on tumor spheroids, 3D structures that self-organize in the presence of an extracellular matrix. Treated spheroids showed decreased lactate production with on-target inhibition confirmed using IHC, demonstrating that HP-MRS can be used to probe treatment response in prostate cancer spheroids and can provide a biomarker for treatment response. Mol Cancer Res; 16(3); 453-60. © 2018 AACR. |
| Journal Title: | Molecular Cancer Research |
| Volume: | 16 |
| Issue: | 3 |
| ISSN: | 1541-7786 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2018-03-01 |
| Start Page: | 453 |
| End Page: | 460 |
| Language: | English |
| DOI: | 10.1158/1541-7786.mcr-17-0458 |
| PROVIDER: | scopus |
| PUBMED: | 29330287 |
| PMCID: | PMC6662159 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2018 -- Source: Scopus |
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