Glioblastoma (GB) is a kind of brain cancer. Previously known as glioblastoma multiforme, it is one of the most deadly types of cancer that starts in the brain. Being the most frequent high-grade primary brain tumor that can occur in adults, it also comes after meningioma as the second most common brain tumor. It has been a challenge to clinicians for years. It hardly occurs in children. The life expectancy of patients is consistently low despite the standard of care and innovative strategies. Neurosurgeons find it challenging to completely remove GB because of the tumor’s heterogeneity and considerable invasiveness, and recurrence is frequent. GB is a glioma stage 4 cancer according to the World Health Organisation (WHO) classification. There is scientific agreement that glioblastoma stem cells (GSCs) are the progenitor/stem-like cells responsible for tumor relapse. These cells serve as precursor cells in the growth and spread of the tumor. They exhibit self-renewal and multi-lineage differentiation characteristics therefore, GSCs are a desirable target for novel therapeutic approaches.
Glioblastoma
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Metformin could be very therapeutic
Recently, Metformin’s anti-cancer qualities have received attention. Patients with type 2 diabetes (T2D) who take metformin have a decreased chance of developing several cancers (including glioblastoma) as well as cancer-related deaths. The anticancer effects of metformin are also aimed toward GSCs, according to multiple investigations on glioblastoma. It has been suggested that it targets the process of oxidative phosphorylation(OXPHOS). Because GSCs can switch between the energy pathways of glycolysis and oxidative phosphorylation, metabolic flexibility may be a fundamental factor in metformin’s lack of efficacy in clinical trials thus far. However, GSCs treated with metformin exhibit a comparable and non-additive suppression of proliferation to that attained by pharmacologically inhibiting the activity of the transmembrane form of Chloride Intracellular Channel 1 (tmCLIC1). Our earlier research has clearly shown how tmCLIC1 contributes to the development of GB both in vitro and in vivo.
Recently, a study was carried out by a group of scientists to identify tmCLIC1 as a special metformin membrane interactor in GSCs by fusing structural and functional studies in vitro and in vivo. For the in vitro experiment, primary cultures of human glioma stem cells (GSCs), designated GBM1, GBM2, and GBM3, were identified and kept alive. Also, Wild type Zebra fish embryos which were transplanted with GSC cells were used. Reagents, as applied to the experiment, were applied. Cells were treated with metformin and observed. For the in vivo experiment, laboratory mice who were injected with GCS cells were utilized. Metformin was administered, and analysis was carried out. On result analysis, The investigation revealed that in GBMM cells, tmCLIC1 is the primary membrane interactor for metformin. The antineoplastic action of the biguanide compound was blocked both in vitro and in vivo by metformin’s inability to bind to tmCLIC1.
Clinical significance
The receptor tmCLIC1 is an effective pharmaceutical target for the therapy of GB due to its precise localization and enrichment at the GSC plasma membrane. Drugs like metformin designed to block tmCLIC1 would distinguish between and preferentially target GSCs and would have fewer adverse effects on the central nervous system.
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Conclusion
Even after receiving regular medical care, glioblastoma remains one of the deadliest solid tumors. The experiment conducted provided enlightenment about how metformin can halt the proliferation of glioblastoma. Future research seeking to strengthen metformin-tmCLIC1 interaction will increase the capability to target glioma stem cells unmistakably.
