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
DOI/URL:
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
Altmetric Score