Arginine Metabolism Is Modulated By Androgen Signalling And Prostate Cancer Progression

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 Conclusions: Arginine is potentially an important aspect of prostate cancer metabolism. Arg targeted therapies may best be suited towards earlier stage tumors and Arg metabolism characterization may have potential as a biomarker of progression to AI prostate cancer. Citation Format: De-Xue Fu, Hubert Huang, Jee-Hoon Song, Min Xu, Lucy Liu, Mohamad Afnan Khan, Krish Chandrasekaran, Arif Hussain, Ganesh Sriram, Mohummad M. Siddiqui. Arginine metabolism is modulated by androgen signalling and prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4414. doi:10.1158/1538-7445.AM2017-4414