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Androgen receptor (AR) activation is the primary driving factor in prostate cancer which is initially responsive to castration but then becomes resistant (castration-resistant prostate cancer (CRPC)). CRPC cells still retain the functioning AR which can be targeted by other therapies. A recent promising development is the use of inhibitors (Epi-1) of protein-protein interaction to inhibit AR-activated signalling. Translating novel therapies into the clinic requires sensitive early response indicators. Here potential response markers are explored. Growth inhibition of prostate cancer cells with flutamide, paclitaxel, and Epi-1 was measured using the MTT assay. To simulate choline-PET scans, pulse-chase experiments were carried out with [3H-methyl]choline and proportion of phosphorylated activity was determined after treatment with growth inhibitory concentrations of each drug. Extracts from treated cells were also subject to 31P-NMR spectroscopy. Cells treated with flutamide demonstrated decreased [3H-methyl]choline phosphorylation, whilst the proportion of phosphorylated [3H-methyl]choline that was present in the lipid fraction was increased in Epi-1-treated cells. Phospholipid breakdown products, glycerophosphorylcholine and glycerophosphoethanolamine levels, were shown by 31P-NMR spectroscopy to be decreased to undetectable levels in cells treated with Epi-1. LNCaP cells responding to treatment with novel protein-protein interaction inhibitors suggest that 31P-NMR spectroscopy may be useful in detecting response to this promising therapy.

Original publication

DOI

10.1155/2017/4793465

Type

Journal article

Journal

Biomed Res Int

Publication Date

2017

Volume

2017

Keywords

Cell Line, Tumor, Cell Proliferation, Choline, Flutamide, Humans, Male, Paclitaxel, Phospholipids, Phosphorylation, Propane, Prostatic Neoplasms, Castration-Resistant, Proton Magnetic Resonance Spectroscopy, Treatment Outcome, Tritium