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Spermine is a natural suppressor of AR signaling in castration-resistant prostate cancer.

Published:25 July 2023 DOI: PMID: 37453063
Xiao Li, Fei Li, Fei Ye, Haotian Guo, Wentao Chen, Jia Jin, Yiran Wang, Pengfei Dai, Huili Shi, Hongru Tao, Wenzhen Dang, Yiluan Ding, Mingchen Wang, Hualiang Jiang, Kaixian Chen, Naixia Zhang, Dong Gao, Yuanyuan Zhang, Cheng Luo

Abstract

In castration-resistant prostate cancer (CRPC), clinical response to androgen receptor (AR) antagonists is limited mainly due to AR-variants expression and restored AR signaling. The metabolite spermine is most abundant in prostate and it decreases as prostate cancer progresses, but its functions remain poorly understood. Here, we show spermine inhibits full-length androgen receptor (AR-FL) and androgen receptor splice variant 7 (AR-V7) signaling and suppresses CRPC cell proliferation by directly binding and inhibiting protein arginine methyltransferase PRMT1. Spermine reduces H4R3me2a modification at the AR locus and suppresses AR binding as well as H3K27ac modification levels at AR target genes. Spermine supplementation restrains CRPC growth in?vivo. PRMT1 inhibition also suppresses AR-FL and AR-V7 signaling and reduces CRPC growth. Collectively, we demonstrate spermine as an anticancer metabolite by inhibiting PRMT1 to transcriptionally inhibit AR-FL and AR-V7 signaling in CRPC, and we indicate spermine and PRMT1 inhibition as powerful strategies overcoming limitations of current AR-based therapies in CRPC.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
SPERMINE TETRAHYDROCHLORIDE 306-67-2 C10H30Cl4N4 339 suppliers $11.00-$10550.00
SPERMINE TETRAHYDROCHLORIDE 306-67-2 C10H30Cl4N4 339 suppliers $11.00-$10550.00
SPERMINE TETRAHYDROCHLORIDE 306-67-2 C10H30Cl4N4 339 suppliers $11.00-$10550.00
SPERMINE TETRAHYDROCHLORIDE 306-67-2 C10H30Cl4N4 339 suppliers $11.00-$10550.00

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