Diarrhoea Drug drive Tumour Cells to Death

Diarrhoea drug Loperamide could support the treatment of brain tumours. Our lymphocytes usually have no chance against stubborn cancer cells.

The research team at Goethe University Frankfurt uncovered the mechanism of action. The active ingredient of the popular diarrhoea drug loperamide could support the treatment of brain tumours.

Researchers at the Goethe University in Frankfurt have shown that loperamide acts against glioblastoma cells in cell culture. Glioblastoma is a highly aggressive and usually fatal form of cancer in children and adults that reacts poorly to chemotherapy drugs. The researchers have published their respective results in the specialist journal “Autophagy”.

Cells eat themselves up.

Indications that the diarrhoea drug loperamide could be used in brain tumours therapy found the working group working with Dr Sjoerd van Wijk from the Institute for Experimental Tumor Research in Pediatrics Goethe University two years ago. According to the Science Information Service, it has deciphered the mechanism of action and thus opens up options for new treatment strategies.

In individual tumour cells, loperamide leads to a stress reaction in the so-called endoplasmic reticulum (ER). This cell organelle is responsible for essential steps in protein synthesis in the body, the researchers told. The ER stress triggers autophagy, which takes it to the edge of the cancer cells’ death.

Autophagy is a natural process in our body in which the valuable parts of damaged or superfluous cell components are “recycled”, explains the research group. For example, the cell’s survival can be ensured in the event of a lack of nutrients. However, in the case of specific tumour cells, so much material is broken down through autophagy that they cannot survive and die. In the case of glioblastoma cells, this can be supported with the diarrhoea drug loperamide.

A Special Transcription Factor is Critical.

According to the researchers in the subject, the “activating transcription factor” ATF4 plays a crucial role in initiating autophagy-dependent cell death in glioblastoma cells. It begins the breakdown of the ER membranes and thus, the entire endoplasmic reticulum of the cells. “Conversely, if there is a blockage of ATF4, significantly fewer cells of a tumour cell culture die after injecting loperamide,” says van Wijk, ascertaining the control results.

The working group could also detect the ER debris in the body’s degradation cells under the powerful electron microscope. “ER degradation, which is reticulophagy, makes a visible contribution to the cell death of glioblastoma cells,” says van Wijk.

Diarrhoea medication could also help with dementia.

The death induced by loperamide cell of glioblastoma cells could help develop new therapeutic approaches to treat this severe cancer. “Our findings open up new and exciting possibilities for other diseases in which ER breakdown is impaired, such as nerve cell diseases, dementia and other types of tumours,” said van Wijk. However, before loperamide can be used to treat glioblastomas or other diseases, some work is necessary.