Targeting Breast Cancer with N-Acetyl-D-Glucosamine: Integrating Machine Learning and Cellular Assays for Promising Results


Baysal Ö., Genç D., Silme R. S., Kırboğa K. K., Çoban D., Abdul Ghafoor N., ...Daha Fazla

Diğer, ss.1-26, 2023

  • Yayın Türü: Diğer Yayınlar / Diğer
  • Basım Tarihi: 2023
  • Sayfa Sayıları: ss.1-26
  • İstanbul Üniversitesi Adresli: Evet

Özet

Early diagnosis of breast cancer can reduce prognosis and mortality rates, but alternative treatments are needed. We studied the effect of N-acetyl-D-glucosamine (D-GlcNAc) on breast cancer using machine learning and cell assays. MCF-7 and 4T1 cell lines (ATCC) were cultured in the presence and absence of varying concentrations of D-GlcNAc (0.5 mM, 1 mM, 2 mM, and 4 mM) for 72 hours. A xenograft mouse model for breast cancer was established by injecting 4T1 cells into mammary glands. D-GlcNAc (2 mM) was administered intraperitoneally to mice daily for 28 days, and histopathological effects were evaluated at pre-tumoral and post-tumoral stages. Treatment with 2 mM and 4 mM D-GlcNAc significantly decreased cell proliferation rates in MCF-7 and 4T1 cell lines and increased Fas expression. The number of apoptotic cells was significantly higher than in untreated cell cultures (P < 0.01 - P < 0.0001). D-GlcNAc administration also considerably reduced tumour size, mitosis, and angiogenesis in the post-treatment group compared to the control breast cancer group (P < 0.01 - P < 0.0001). Molecular docking/dynamic analysis revealed a high binding affinity of D-GlcNAc to the marker protein HER2, which is involved in tumor progression and cell signalling. Our study demonstrates the positive effect of D-GlcNAc administration on breast cancer cells, leading to increased apoptosis and Fas expression in the malignant phenotype. The binding affinity of D-GlcNAc to HER2 suggests a potential mechanism of action. These findings contribute to understanding D-GlcNAc as a potential anti-tumor agent for breast cancer treatment.