Autophagy: New results for old medicines! The anti-diarrhea drug "Lopedamine" may hopefully drive cancer cell death!

January 4, 2021 // -- Two years ago, scientists from the University of Goethe found evidence that the anti-diarrhea drug loperamide may be used to induce death in the cell line of glioblastoma, and in a recent study published in the international journal Autotahagy, the same group of researchers revealed the molecular mechanisms by which the drug lopedide drives cancer cell deaths, and that the results may help develop new treatments for cancer.
In certain types of tumor cells, giving the drug lopedamine causes a stress response in the endosome web, a cellular device that is a key step in the synthesis of complex proteins in the body's cells; Autophagy-dependent cell death processes occur; under normal circumstances, autophagy can help regulate normal metabolic processes and break and recycle key parts of excess cell components that damage or ensure cell survival, such as in the case of nutritional deficiencies; however, in specific tumor cells, overactivation of autophagy can destroy so many cellular materials that it can no longer survive.
Photo Source: Svenja Zielke et al researcher van Wijk says: 'Our results on cell line show that autophagy supports the treatment of glioblastoma, a malignant and fatal type of cancer in children and adults that can produce poor responses to chemotherapy; In this study, the researchers were one of the most important factors that linked endotrogenic mesh stress response to the degradation of endotrogen mesh, i.e. the production of "activative transcription factor" ATF4 increased under the influence of endotogenous mesh pressure and the drug lopedinamine, which induced the destruction of endotrative mesh and endotrnet.
In contrast, blocking ATF4 induces fewer tumor cell deaths when loptatin is added, and the researchers used electroscopic analysis to analyze cells receiving the drug loptamin that detected fragments of the endoscopic mesh;
lopedin only induces autophagy, not the death of other cells, such as embryonic fibroblasts in mice.
normally, when used as a laxative, loptadine binds to a specific binding point in the intestine and is not absorbed by the intestine, so the drug is harmless.
Death of glioblastoma induced by the drug lopyptamine may help develop new therapeutic strategies for treating severe forms of cancer; however, the findings of this paper do not raise new possibilities for treating other diseases that have been damaged by endoblast degradation, such as neurological diseases, dementia, or other types of tumors.
However, when loptamin is actually used to treat glioblastoma or other diseases, researchers will need to do more research; in the future, researchers will continue to delve deeper into how Lopedamine is transported across the brain barrier to the brain, nanoparticles may be a viable option, and researchers are now looking at how the effects of the drug lopedamine are enhanced by identifying substances that induce autophagy in the endoblastamine.
original source: Svenja Zielke et al, ATF4 links ER stress with reticulophagy in glioblastoma cells, Autophagy (2020). DOI:10.1080/15548627.2020.1827780。