Metabolomic profiling to evaluate the efficacy of proxalutamide, a novel androgen receptor antagonist, in prostate cancer cells

SummaryProxalutamide is a newly developed androgen receptor (AR) antagonist for the treatment of castration-resistant prostate cancer (PCa) that has entered phase III clinical trials. In the present study, we intended to elucidate the antitumor efficacy of proxalutamide through the metabolomic profiling of PCa cells. Two AR-positive PCa cell lines and two AR-negative PCa cell lines were investigated. Cell viability assays based on ATP quantitation were conducted. LC-Q/TOF-MS was used to analyze intracellular metabolites before or after the administration of proxalutamide and two other clinical AR antagonists (bicalutamide and enzalutamide). The results of this study showed that the inhibitory effect of proxalutamide on PCa cell proliferation was better than that of bicalutamide and enzalutamide, and proxalutamide preferentially affected AR-positive PCa cells over AR-negative cells. The metabolic composition of PCa cells changed significantly after proxalutamide administration, and these changes in response to proxalutamide were significantly different from those in the presence of the two other AR antagonists. In AR-positive cells, proxalutamide significantly decreased the intracellular levels of glutamine, glutamate, glutathione, cysteine, glycine, aspartate, uridine, cytidine and thymidine. However, the effects of the two other antagonists on these discriminant metabolites were ambiguous, and no changes in these metabolites were found in AR-negative cells. Our findings indi...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 13 July 2020Source: Pathology - Research and PracticeAuthor(s): Yu-Peng Wu, Zhi-Bin Ke, Fei Lin, Yao-An Wen, Sheng Chen, Xiao-Dong Li, Shao-Hao Chen, Xiong-Lin Sun, Jin-Bei Huang, Qing-Shui Zheng, Xue-Yi Xue, Yong Wei, Ning Xu
Source: Pathology Research and Practice - Category: Pathology Source Type: research
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Source: Disease Markers - Category: Laboratory Medicine Tags: Dis Markers Source Type: research
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Source: The Doctors Lounge - Oncology - Category: Cancer & Oncology Tags: Oncology, Pathology, Pharmacy, Urology, Journal, Source Type: news
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Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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Source: the Mail online | Health - Category: Consumer Health News Source Type: news
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Source: Infectious Agents and Cancer - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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