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  11. Brucine Suppresses Malignant Progression Of Prostate Cancer By Decreasing Sarcosine Accumulation Via Downregulation Of Gnmt In The Glycine/sarcosine Metabolic Pathway.

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

Long Miao1, Yang Liu2, Wei Chen1

  • 1Department of Urology, Xuzhou No. 1 People's Hospital, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, 221004, PR China.

Cell Biochemistry and Biophysics
|June 14, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Brucine, a glycine antagonist, inhibits prostate cancer (PCa) progression by reducing sarcosine levels and downregulating glycine N-methyltransferase (GNMT) expression. This study reveals novel antitumor mechanisms for brucine in PCa treatment.

Area of Science:

  • Oncology
  • Metabolomics
  • Pharmacology

Background:

  • Prostate cancer (PCa) is a major cause of cancer mortality in men, with amino acid (AA) metabolism disruptions contributing to its progression.
  • Brucine, a glycine antagonist, has demonstrated potential antitumor effects, warranting further investigation into its mechanisms in PCa.

Purpose of the Study:

  • To explore the antitumor impact of brucine on prostate cancer (PCa).
  • To investigate the mechanisms by which brucine regulates amino acid (AA) metabolic pathways in PCa.

Main Methods:

  • Utilized the DU-145 PCa cell line and RWPE-1 normal cells for various assays (CCK8, wound healing, Transwell, EDU, TUNEL, flow cytometry, Western blot, UPLC-MS/MS).
  • Employed network pharmacological analysis to identify brucine's anticancer mechanisms.
Keywords:
Amino acid metabolismApoptosisBrucineProliferation

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  • Analyzed glycine N-methyltransferase (GNMT) expression in PCa tissues and The Cancer Genome Atlas (TCGA) database.

    • Main Results:

    • Brucine significantly decreased PCa cell viability, proliferation, invasion, and migration while promoting apoptosis, in a dose-dependent manner.
    • Brucine treatment reduced sarcosine (Sar) levels and downregulated GNMT expression in DU-145 cells, without affecting SARDH.
    • Elevated GNMT expression was observed in PCa tissues and TCGA data; recombinant GNMT partially reversed brucine's inhibitory effects.

    Conclusions:

    • Brucine exhibits significant antitumor effects in prostate cancer (PCa) by targeting amino acid metabolism.
    • Brucine downregulates GNMT, reducing sarcosine accumulation and inhibiting PCa progression.
    • These findings offer new insights into brucine's therapeutic potential for PCa.
    Prostate cancer