RESUMO
Glioblastoma Multiforme (GBM), an aggressive brain tumor (grade-IV astrocytoma), poses treatment challenges. Poor prognosis results from the rapid growth, highlighting the role of EIF4A3 in regulating non-coding RNAs. EIF4A3 promotes the expression of several non-coding RNAs, viz, Circ matrix metallopeptidase 9 (MMP9), a prominent oncogene, by interacting with the upstream region of the circMMP9 mRNA transcript and acts on cell proliferation, migration, and invasion of GBM. However, research shows that EIF4A3 knockdown inhibits glioblastoma progression and increases apoptosis. In this study, we explored the efficiency of the phytochemicals from plants like Withania somnifera and Castanea sativa with potential anti-glioblastoma effects as obtained from the Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT) database. Consequently, we have performed a virtual screening of the compounds against the protein EIF4A3. We further investigated the efficiency of the shortlisted compounds based on docking scores evaluated using GOLD, AutoDock4.2, LeDock, and binding free energy analyses using Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA). Among the phytochemicals studied so far, several Withania-specific compounds from Withania somnifera and a single dietary compound, viz., Thiamine from Castanea sativa, have exhibited comparatively good blood-brain barrier permeability, significant binding affinity towards the EIF4A3, and good ADMET properties. Furthermore, we have verified the interaction stability of the lead molecules with EIF4A3 using MD simulations. Thus, the present study offers an opportunity to develop drug candidates targeting glioblastoma caused by EIF4A3 over-expression, integrating phytotherapy into precision oncology to create tailored and precise natural treatment strategies for cancer.Communicated by Ramaswamy H. Sarma.
RESUMO
Background: Glioblastoma multiforme, commonly known as GBM or glioblastoma is a grade IV astrocytoma. Brain tumors are difficult to treat and lead to poor prognosis and survival in patients. Gliomas are categorized into four different grades among which GBM is the worst grade primary brain tumor with a survival of less than a year. The genomic heterogeneity of the brain tumor results in different profiles for patients diagnosed with glioblastoma. Precision medicine focuses on this specific tumor type and suggests specialized treatment for better prognosis and overall survival (OS). Purpose: With the recent advancements in Genome-Wide Studies (GWS) and various characterizations of brain tumors based on genetic, transcriptomic, proteomic, epigenetic, and metabolomics, this review discusses the advancements and opportunities of precision medicine therapeutics, drugs, and diagnosis methods based on the different profiles of glioblastoma. Methods: This review has exhaustively surveyed several pieces of works from various literature databases. Conclusion: It is evident that most primary brain tumors including glioblastoma require specific and precision therapeutics for better prognosis and OS. In present and future, molecular understanding and discovering specific therapies are essential for treatment in the field of neurooncology.
