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

Male Humans Receptors, Androgen / metabolism Prostatic Neoplasms, Castration-Resistant / drug therapy Spermine / pharmacology Signal Transduction Androgen Receptor Antagonists / therapeutic use Cell Line, Tumor Protein-Arginine N-Methyltransferases / genetics Repressor Proteins / metabolism
AR-FL AR-V7 CP: Cancer CRPC Metabolite PRMT1 Spermine

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
25 07 2023
Historique:
received: 14 09 2022
revised: 04 04 2023
accepted: 26 06 2023
medline: 31 7 2023
pubmed: 15 7 2023
entrez: 15 7 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2023.112798 PMID: 37453063
pubmed: 37453063
pii: S2211-1247(23)00809-4
doi: 10.1016/j.celrep.2023.112798
pii:
doi:

Substances chimiques

Receptors, Androgen 0
Spermine 2FZ7Y3VOQX
Androgen Receptor Antagonists 0
PRMT1 protein, human EC 2.1.1.319
Protein-Arginine N-Methyltransferases EC 2.1.1.319
Repressor Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

112798

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Xiao Li (X)

School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China.

Fei Li (F)

State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.

Fei Ye (F)

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China; College of Life Sciences and Medicine, Zhejiang SciTech University, Hangzhou 310018, China.

Haotian Guo (H)

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; China Pharmaceutical University, Nanjing 210009, P.R. China.

Wentao Chen (W)

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China.

Jia Jin (J)

College of Life Sciences and Medicine, Zhejiang SciTech University, Hangzhou 310018, China.

Yiran Wang (Y)

School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Pengfei Dai (P)

University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China; State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.

Huili Shi (H)

University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China; State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.

Hongru Tao (H)

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Wenzhen Dang (W)

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Yiluan Ding (Y)

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Mingchen Wang (M)

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Hualiang Jiang (H)

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Kaixian Chen (K)

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Naixia Zhang (N)

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Dong Gao (D)

State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: dong.gao@sibcb.ac.cn.

Yuanyuan Zhang (Y)

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China. Electronic address: yyzhang@simm.ac.cn.

Cheng Luo (C)

School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China; School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China; China Pharmaceutical University, Nanjing 210009, P.R. China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528437, China. Electronic address: cluo@simm.ac.cn.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Spermine is a natural suppressor of AR...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteurs aux androgènes › Spermine is a natural suppressor of AR...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Tumeurs prostatiques résistantes à la castration › Spermine is a natural suppressor of AR...
questionsmedicales.fr › Composés chimiques organiques › Amines › Polyamines › Spermine › Spermine is a natural suppressor of AR...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Spermine is a natural suppressor of AR...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hormones, substituts d'hormones et antagonistes d'hormones › Antihormones › Antagonistes des androgènes › Antagonistes du récepteur des androgènes › Spermine is a natural suppressor of AR...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Spermine is a natural suppressor of AR...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › Protein Methyltransferases › Protein-arginine N-methyltransferases › Spermine is a natural suppressor of AR...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Spermine is a natural suppressor of AR...