Supp. Figure 5 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:10.1158/1541-7786.22512912.v1

15417786mcr170458-sup-188213_2_supp_4382076_7z5r2m.pdf (2.58 MB)

Supp. Figure 5 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

Time-lapse images of spheroid formation. LnCAP cells were grown on a 1:1 mixture of sodium alginate and matrigel in ultra-low adhesion 96-well plates. Time-lapse images were acquired using a 10X objective on the Incucyte cell imager platform located in a humidified cell culture chamber. Scale bar = 1mm

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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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