Molecular Docking Analysis of Bacoside A with Selected Signalling Factors Involved in Glioblastoma

Abstract

Glioblastoma is the malignant tumor affecting the central nervous system. Despite the advancement in treatment modalities, presence of blood-brain barrier, recurrence after surgical removal, resistance to radiotherapy and chemotherapy remain the major obstacles for long term survival of the patients. In this context, finding suitable therapeutics which have anticancer potential and are nontoxic might be useful to improve the overall survival of GBM. Plant products are safer, nontoxic and cheaper when compared to the chemotherapeutic drugs in trend which are expensive and highly toxic, owing to their systemic effects. Bacoside A (BA) is one such plant constituent isolated from Bacopa monnieri which offers neuroprotection and possesses anticancer potential. The present investigation elucidates the specific interaction of BA with various cell surface receptors, signal transduction proteins, effector proteins and transcription factors involved in glioblastoma signalling such as EGFR/Ras/Raf/MAPK pathway, Notch signalling and Wnt-beta catenin signalling through molecular docking studies. The interaction between BA and the target proteins of glioblastoma were analysed through the Glide module (Version 6.5) of Schrodinger Suite (2015) software. According to the results of molecular docking, jagged-1 ligands interact with BA with stronger affinity and Frizzled receptors interact with least affinity in terms of glide score. The results indicate that BA interacts well with the polar amino acids such as Asn, Trp, Arg, Ser, Thr, Tyr, Gln, Asp, Lys and Glu. The ligand also showed interactions with specific hydrophobic amino acids such as Val, Ala and Leu in all the protein targets studied. The in vitro cytotoxicity studies reveal the cytotoxic potential of BA on the U87MG glioblastoma cell line. This study warrants further investigation to elucidate modulations on cell signalling pathways resulting from the specific BA-target interactions in glioblastoma.