Supp. Figure 1 from Targeted AKT Inhibition in Prostate Cancer Cells and Spheroids Reduces Aerobic Glycolysis and Generation of Hyperpolarized [1-13C] Lactate

Tee, Sui Seng; Suster, Izabela; Truong, Steven; Jeong, Sangmoo; Eskandari, Roozbeh; DiGialleonardo, Valentina; Alvarez, Julio A.; Aldeborgh, Hannah N.; Keshari, Kayvan R.

doi:10.1158/1541-7786.22512927.v1

Supp. Figure 1 from Targeted AKT Inhibition in Prostate Cancer Cells and Spheroids Reduces Aerobic Glycolysis and Generation of Hyperpolarized [1-<sup>13</sup>C] Lactate

https://doi.org/10.1158/1541-7786.22512927

journal contribution

posted on 2023-04-03, 16:44 authored by Sui Seng Tee, Izabela Suster, Steven Truong, Sangmoo Jeong, Roozbeh Eskandari, Valentina DiGialleonardo, Julio A. Alvarez, Hannah N. Aldeborgh, Kayvan R. Keshari

<p>Proton NMR spectra of LnCAP cell extracts treated either with DMSO or 1uM MK2206 for 24 hr. Co-factor concentrations were quantified as a ratio between the resonance for the lone hydrogen atom on the five membered ring of the adenine moiety in NAD+ that resonates at 8.435 ppm and NADH at 8.486 ppm. Extractions of cells were performed as described in the materials section.</p>

Funding

NIH

NCI

History

Related Materials

1.
DOI - Is supplement to Targeted AKT Inhibition in Prostate Cancer Cells and Spheroids Reduces Aerobic Glycolysis and Generation of Hyperpolarized [1-13C] Lactate

ARTICLE 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 NAD+/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.