Abstract 4414: Arginine metabolism is modulated by androgen signalling and prostate cancer progression

• Published in: Cancer research (Chicago, Ill.) Ill.), 2017-07, Vol.77 (13_Supplement), p.4414-4414
• Main Authors: Fu, De-Xue, Huang, Hubert, Song, Jee-Hoon, Xu, Min, Liu, Lucy, Khan, Mohamad Afnan, Chandrasekaran, Krish, Hussain, Arif, Sriram, Ganesh, Siddiqui, Mohummad M.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2017-4414

Background: Metabolic reprogramming has been described as one of the hallmarks of cancer. A pathway of promise in prostate cancer management is arginine (Arg) metabolism. Phase 2 clinical trials are underway to study arginine deprivation as a treatment of prostate cancer. However, heterogeneous response has been noted and further studies are needed to better identify prostate tumors most reliant on Arg metabolism. The aim of this study was to investigate if Arg metabolism was associated with androgen signalling and prostate cancer progression from androgen dependent (AD) to androgen independent (AI) phenotype. Methods: The LNCaP prostate cancer cell line was used. Four sets of conditions were tested: LNCaP control, LNCaP in the presence of dihydrotestosterone (DHT), LNCaP with MDV3100 (an AR inhibitor), and a subline of LNCaP (CSS90) which has become AI. MTT viability assay was used to assess cell viability. The Seahorse XF bioenergetics analyzer was used to measure metabolic oxygen consumption. Gas Chromatography and Mass Spectroscopy (GC/MS) was used for metabolomics characterization. Results: LNCaP cells at a baseline are Arg-dependent. Arg starvation led to a 63% decrease in LNCaP cell viability (p