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. 2016:12:120.
doi: 10.1007/s11306-016-1055-0. Epub 2016 Jun 30.

Response of Degarelix treatment in human prostate cancer monitored by HR-MAS 1H NMR spectroscopy

Basetti Madhu  1 , Greg L Shaw  2 , Anne Y Warren  3 , David E Neal  4 , John R Griffiths  1
Affiliations

Response of Degarelix treatment in human prostate cancer monitored by HR-MAS 1H NMR spectroscopy

Basetti Madhu et al. Metabolomics. 2016.

Abstract

Introduction: The androgen receptor (AR) is the master regulator of prostate cancer cell metabolism. Degarelix is a novel gonadotrophin-releasing hormone blocker, used to decrease serum androgen levels in order to treat advanced human prostate cancer. Little is known of the rapid metabolic response of the human prostate cancer tissue samples to the decreased androgen levels.

Objectives: To investigate the metabolic responses in benign and cancerous tissue samples from patients after treatment with Degarelix by using HRMAS 1H NMR spectroscopy.

Methods: Using non-destructive HR-MAS 1H NMR spectroscopy we analysed the metabolic changes induced by decreased AR signalling in human prostate cancer tissue samples. Absolute concentrations of the metabolites alanine, lactate, glutamine, glutamate, citrate, choline compounds [t-choline = choline + phosphocholine (PC) + glycerophosphocholine (GPC)], creatine compounds [t-creatine = creatine (Cr) + phosphocreatine (PCr)], taurine, myo-inositol and polyamines were measured in benign prostate tissue samples (n = 10), in prostate cancer specimens from untreated patients (n = 7) and prostate cancer specimens from patients treated with Degarelix (n = 6).

Results: Lactate, alanine and t-choline concentrations were significantly elevated in high-grade prostate cancer samples when compared to benign samples in untreated patients. Decreased androgen levels resulted in significant decreases of lactate and t-choline concentrations in human prostate cancer biopsies.

Conclusions: The reduced concentrations of lactate and t-choline metabolites due to Degarelix could in principle be monitored by in vivo 1H MRS, which suggests that it would be possible to monitor the effects of physical or chemical castration in patients by that non-invasive method.

Keywords: Cancer; Degarelix; HR-MAS; Metabolism; Metabolomics; NMR; Prostate.

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Figures

Fig. 1
Fig. 1
H&E sections from the patient prostate tissue samples
Fig. 2
Fig. 2
LC Model fittings of water suppressed HRMAS 1H NMR spectra from prostate tissue samples. Residuals between the observed and fitted spectrum are also shown on each of the spectra. (Gln glutamine Glu-Glutamate, Cit citrate, Cr creatine, PCr phosphocreatine, Cho choline, PC phosphocholine, GPC glycerophosphocholine, Tau taurine, myo-Ino myo-Inositol)
Fig. 3
Fig. 3
Results from Principal Component Analysis (top left and right panels) and OPLS-DA (bottom left and right panels). Green dots on the left panels are samples from untreated patients (C) and blue dots are samples from Degarelix-treated patients (T)
Fig. 4
Fig. 4
Lactate, t-choline and t-creatine metabolite changes in benign, untreated and Degarelix-treated prostate cancer
See this image and copyright information in PMC

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