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

15417786mcr170458-sup-188213_2_supp_4382071_zz5r2l.pdf (58.99 kB)

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

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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

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.

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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.

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Keywords

Cancer Prevention Identification of new risk factors Cell Signaling Protein serine-threonine kinases Genitourinary Cancers Prostate cancer

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