CONICET | Buscador de Institutos y Recursos Humanos

Autophagy is a highly conserved process that plays an essential role in fast adaptation to changing environmental conditions and cellular remodeling during development. Therefore, it is not surprising that changes in autophagic flow are associated with the onset and progression of various pathologies. However, despite the clear therapeutic potential of pharmacological modulators of autophagic flux, there are currently very few examples. Here we show that a family of drugs used in the treatment of psychiatric disorders interferes with autophagic flow. Treatment of cells with these compounds results in a significant increase in the levels of specific autophagosomal markers and a concomitant blockage of degradation of autophagic cargo. Our observations describe a new function for this group of compounds that may have therapeutic implications outside the field of psychiatric disorders and in particular in the treatment of malignant cells that take advantage of the autophagic pathway to survive stress conditions. In this regard, we show that the compounds tested increase the cytotoxic effect of doxorubicin, an agent used in the treatment of a wide variety of cancers. Finally, it is worth noting that these compounds have been used in the clinic for many years, and a wealth of information is available on its bioavailability, toxicity and therapeutic doses. Therefore, their use in an alternative setting would avoid one of the major time and effort consuming issues in drug discovery, namely gaining approval for a new chemical entity.