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The research group led by Dr Sjoerd van Wijk from the Institute of Experimental Cancer Research in Paediatrics at Goethe University already two years ago found evidence indicating that the anti-diarrhoea drug loperamide could be used to induce cell death in glioblastoma cell lines. They have now deciphered its mechanism of action and, in doing so, are opening new avenues for the development of novel treatment strategies.
When cells digest themselves
In certain types of tumour cells, administration of loperamide leads to a stress response in the endoplasmic reticulum (ER), the cell organelle responsible for key steps in protein synthesis in the body. The stress in the ER triggers its degradation, followed by self-destruction of the cells. This mechanism, known as autophagy-dependent cell death occurs when cells undergo hyperactivated autophagy. Normally, autophagy regulates normal metabolic processes and breaks down and recycles the valuable parts of damaged or superfluous cell components thus ensuring the cell's survival, for example in the case of nutrient deficiency. In certain tumour cells, however, hyperactivation of autophagy destroys so much cell material that they are no longer capable of surviving.