ABERRANT N-GLYCOSYLATION REGULATES INVASION OF MG-63 CELLS THROUGH EXTRACELLULAR MATRIX REMODELING

  • SARMILA HANIM MUSTAFA Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Institute of Medical and Molecular Biotechnology, Universiti Teknologi MARA, Cawangan Selangor, Kampus Sungai Buloh, 47000 Sungai Buloh, Selangor, Malaysia.
  • MUDIANA MUHAMAD Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universiti Teknologi MARA, Cawangan Selangor, Kampus Sungai Buloh, 47000 Sungai Buloh, Selangor, Malaysia.
  • SHARANIZA AB-RAHIM Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universiti Teknologi MARA, Cawangan Selangor, Kampus Sungai Buloh, 47000 Sungai Buloh, Selangor, Malaysia.

Abstract

Objective: Despite advances in multimodal therapy, osteosarcoma (OS) still imposes big challenge due to its high rate of metastasis. The previous
studies reported that aberrant glycosylation in the cells mediates the invasion of several cancers including OS. However, its mechanism, particularly
N-glycosylation in OS progression, is still poorly understood. Thus, this study aims to investigate the effect of glycosylation inhibitions toward OS cells
invasiveness.
Materials and Methods: Both 1-deoxynojirimycin (DNJ) and 1-deoxymannojirimycin (1-DMJ) were used to inhibit the activities of
alpha-glucosidase-I/II and alpha-1,2-mannosidase, respectively. Invasion assay and real-time polymerase chain reaction (PCR) (quantitative PCR
[qPCR]) analysis of extracellular matrix-related genes were performed at post 24 h of treatment with the inhibitors, 0.5 mM 1-DNJ and 0.5 mM 1-DMJ,
respectively, on the OS cell line, MG-63.
Results: Results showed that the inhibition of N-glycosylation with 1-DNJ decreases the invasion rate of MG-63 cells while the inhibition of
N-glycosylation by 1-DMJ caused the invasion rate of MG-63 cells to increase. qPCR analysis showed downregulated expression of matrix
metalloproteinase (MMP2) gene in both types of treatments while the expression of its inhibitor, tissue inhibitor of metalloproteinase (TIMP2) was
upregulated in both types of treatments. In this study, MMP9 genes were not detected in both samples; however, the expression of its inhibitor, TIMP1
was downregulated in MG-63 cells treated with 1-DNJ but upregulated in 1-DMJ treated cells.
Conclusion: It is concluded that 1-DNJ reduced the invasion rate in MG-63 cells through downregulation of MMP2 gene which subsequently reduced
degradation of collagen type IV. However, the contrasting effect showed by 1-DMJ requires further investigation to elucidate its underlying mechanism.

Keywords: Extracellular matrix genes, Glycosylation inhibitors, N-glycosylation, Osteosarcoma

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MUSTAFA, S. H., MUHAMAD, M., & AB-RAHIM, S. (2019). ABERRANT N-GLYCOSYLATION REGULATES INVASION OF MG-63 CELLS THROUGH EXTRACELLULAR MATRIX REMODELING. International Journal of Applied Pharmaceutics, 11(5), 75-79. https://doi.org/10.22159/ijap.2019.v11s5.T0053
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