10/30/2026
A medication commonly found in pharmacies for treating diarrhea may have an unexpected effect on one of the deadliest forms of brain cancer. Glioblastoma is an aggressive brain tumor known for its rapid growth, resistance to treatment, and high recurrence rates.
A 2021 study published in the journal Autophagy investigated whether loperamide, an over-the-counter anti-diarrheal drug, and pimozide, an antipsychotic medication, could trigger cell death in human glioblastoma cells. Researchers at Goethe University Frankfurt studied MZ-54 glioblastoma cells and discovered that both medications induced a form of cell death dependent on autophagy, the process cells use to break down and recycle damaged components. Rather than simply blocking cancer cell growth, the drugs disrupted several cellular survival mechanisms simultaneously.
Specifically, loperamide and pimozide caused substantial accumulation of cholesterol and other lipids inside lysosomes, the structures responsible for cellular waste processing. Researchers also observed increased levels of ceramides, glucosylceramides, and sphingoid bases, alongside inhibition of acid sphingomyelinase (SMPD1/ASM), an enzyme involved in lipid metabolism.
These changes contributed to lysosomal membrane permeabilization, allowing enzymes such as cathepsin B to escape into the cytoplasm and promote cancer cell death. Importantly, when researchers knocked out the autophagy-related genes ATG5 and ATG7, both lysosomal damage and cell death were significantly reduced. Cathepsin inhibitors and the antioxidant alpha-tocopherol (vitamin E) also reduced cell death, suggesting that lysosomal enzymes and lipid-related oxidative damage contributed to the effects.
These findings identify a potential strategy for targeting glioblastoma through excessive autophagy and lysosomal disruption.
