The common drug, Loperamide, that is usually prescribed to treat diarrhoea, (brand name immodium) may be a powerful weapon against glioblastoma brain cancer.
In the study, researchers sought to understand the mechanism of action of Loperamide, LOP, which had previously been shown to induce cell death of glioblastoma cells.
In cancer, selective degradation of the endoplasmic reticulum (the cytoplasm of cells which produces proteins) is a type of cellular destruction. Amino acid starvation and various stressors can bring it on and restore cell energy levels.
In this study, researchers explored the ability of loperamide to cause cell death (autophagy) in glioblastoma cells. They found LOP triggers upregulation of the transcription factor ATF4, which increases ER stress markers. This then blocks the formation of abnormal proteins which cause cancer.
The researchers from the paediatric unit of the University of Goethe am Rhein found ATF4 had to be present. Other cancers are now going the be studied and, with brain tumours (GBM, a delivery mechanism is being sought so that the drug can cross the blood brain barrier.
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Reference
- https://www.tandfonline.com/doi/full/10.1080/15548627.2020.1827780