Cell biochemistry and biophysicsJun 14, 2024

Brucine may slow prostate cancer growth by reducing sarcosine levels through lowering GNMT in the glycine/sarcosine pathway

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 13, 2026

Abstract

Brucine treatment resulted in a marked decrease in cell viability and proliferation in prostate cancer cells.

Prostate cancer cells (DU-145) exhibited significantly higher levels of sarcosine compared to normal prostatic epithelial cells (RWPE-1).
Brucine treatment decreased cell viability, proliferation, invasion, and migration of DU-145 cells in a dose-dependent manner.
Brucine promoted apoptosis in DU-145 cells, with a corresponding reduction in sarcosine levels as brucine concentration increased.
Network pharmacology analysis indicated that brucine's anticancer effects may be linked to amino acid metabolism and glycine N-methyltransferase (GNMT) pathways.
GNMT expression was significantly elevated in prostate cancer tissues compared to controls and was downregulated in DU-145 cells following brucine treatment.

Simplified

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.

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Brucine may slow prostate cancer growth by reducing sarcosine levels through lowering GNMT in the glycine/sarcosine pathway

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