Abstract:
Glioblastoma multiforme (GBM) is a tumor of glial origin and is most malignant, aggressive,
and prevalent with highest mortality rate in adult brain cancer. The clinical treatment
available is surgical resection of tumor followed with standard drug Temozolomide (TMZ).
The current standard treatment has major limitations with 50% of patients’ resistance to TMZ
and average survival of 15 months after diagnosis. This underscores the need of investigating
novel potential drugs and their targets in GBM. Rosmarinic acid (RA), natural constituent of
Lamiaceae plants have reported neuropharmacological and anti-cancerous properties.
This study seeks to investigate the binding and interacting potential of rosmarinic acid with
aberrant expressing proteins in GBM. This study evaluates the molecular interaction of
rosmarinic acid to following target protein: Hsp27, EGFR, TNF-α, Annexin A2, IL17A,
galectin-1 as protein-ligand interactions play a vital role in drug design. Automated docking
studies were performed utilizing Autodock4 to provide useful insights into rosmarinic acid
bindings to GBM potential targets. The results show encouraging therapeutic potential of RA
against targeted proteins with strongest interaction and binding affinity to HSP-27 and TNF-a
out of the selected proteins. The docking comparison of RA with standard drug
Temozolomide indicated binding interactions of TMZ with selected targeted proteins. RA
formed more stable conformation with targeted proteins compared to TMZ on the basis of
binding energy and protein ligand orientation.
Uncharacteristic glycosylation has been associated with tumorigenesis and metastasis
mechanisms. Sialic acid sugars attached to glycoproteins and glycolipids upregulation is a
hallmark feature of tumor cell. Glycosylation can also be a potential diagnostic marker as
well as a putative aim for therapy in GBM. The study also predicted the glycosylation sites in
the above targeted proteins employing NetN Glycan software. Whereas protein glycosylation
pattern was also investigated in U87 malignant glioma (U87-MG) cell lines. Moreover,
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differential protein expression between sensitive and resistant variants of U87-MG cell lines
to standard drug TMZ were studied using 2D gel electrophoresis and SDS-PAGE. Protein
spot identification and statistics were performed with the help of Delta2D software. A total of
10 protein spots were identified as differentially expressed. These findings may aid in
understanding the potential role of these proteins and can serve as potential biomarkers and
drug targets for GBM
