Evidence map›Paper›PMID 38877335›Full record

ArticleCell biochemistry and biophysics2024

Brucine Suppresses Malignant Progression of Prostate Cancer by Decreasing Sarcosine Accumulation via Downregulation of GNMT in the Glycine/sarcosine Metabolic Pathway.

Long Miao, Yang Liu, Wei Chen, Chao Gao, Yijing Zhang, Jin Wei, Xiliang Cao

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Article in Cell biochemistry and biophysics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Long Miao *Department of Urology, Xuzhou No. 1 People's Hospital, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, 221004, PR China.
Yang Liu *Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221004, PR China.
Wei ChenDepartment of Urology, Xuzhou No. 1 People's Hospital, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, 221004, PR China.
Chao GaoDepartment of Urology, Xuzhou No. 1 People's Hospital, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, 221004, PR China.
Yijing ZhangDepartment of Urology, Xuzhou No. 1 People's Hospital, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, 221004, PR China.
Jin WeiDepartment of Urology, Xuzhou No. 1 People's Hospital, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, 221004, PR China.
Xiliang CaoDepartment of Urology, Xuzhou No. 1 People's Hospital, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, 221004, PR China. caoxiliang1971@sina.com.

Funding

the Science and Technology Planning Project of Traditional Chinese Medicine, Jiangsu YB2020050
6 · The paper itself

Abstract

Prostate cancer (PCa) remains a leading cause of cancer-related incidence and mortality in men. Disruptions in amino acid (AA) metabolism contribute to the disease progression, with brucine, a glycine antagonist, exhibiting antitumor effects. This study explores the antitumor impact of brucine on PCa and investigates its mechanisms in regulating AA metabolic pathways. The study employed the PCa cell line DU-145, characterized by high sarcosine (Sar) levels, for various assays including Cell Counting Kit-8 (CCK8), wound healing, Transwell, 5-Ethynyl-2'-deoxyuridine (EDU), TdT mediated dUTP Nick End Labeling (TUNEL), flow cytometry, Western blot, and ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Network pharmacological analysis determined the anticancer mechanisms of brucine. Sar levels in DU-145 cells were significantly higher than in normal prostatic epithelial cells RWPE-1. Treatment with brucine resulted in a marked decrease in cell viability, proliferation, invasion, and migration, while promoting apoptosis in a dose-dependent manner. Sar levels decreased with increasing brucine concentration. Network pharmacology analysis linked brucine's anticancer effect to the AA metabolism and glycine N-methyltransferase (GNMT) pathways. GNMT expression in prostate cancer tissues and The Cancer Genome Atlas database was significantly elevated compared to controls. Treatment with brucine led to downregulation of GNMT expression in DU-145 cells without significant effect on sarcosine dehydrogenase (SARDH). Addition of recombinant GNMT partially reversed the inhibitory effects of brucine on DU-145 cells. Treatment with brucine downregulates GNMT expression in DU-145 cells, reducing Sar accumulation and inhibiting tumor progression. These findings provide new insights into the antitumor mechanisms of brucine in PCa.

Indexed as

ApoptosisDown-RegulationGlycineGlycine N-MethyltransferaseProstatic NeoplasmsSarcosineStrychnineAntineoplastic AgentsCell Line, TumorCell MovementCell ProliferationCell SurvivalDisease ProgressionHumansMaleMetabolic Networks and PathwaysAntineoplastic AgentsbrucineGlycineGlycine N-MethyltransferaseGNMT protein, humanSarcosineStrychnineAmino acid metabolismApoptosisBrucineProliferationProstate cancer

Identifiers

PMID38877335

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