Tilorone Acts as a Lysosomotropic Agent in Fibroblasts

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Abstract
Tilorone, an amphiphilic cationic compound with antiviral activity perturbed the lysosomal system. In cultured [human] fibroblasts tilorone induced storage of sulfated glycosaminoglycans, enhanced secretion of precursor forms of lysosomal enzymes, inhibited intracellular proteolytic maturation of lysosomal enzymes, and inhibited receptor-mediated endocytosis of lysosomal enzymes. In isolated lysosomes tilorone was found to increase pH and to abolish the ATP-dependent acidification. Tilorone apparently acts like a weak base that accumulates in acid compartments of the cells, raises the pH therein and interferes with lysosomal catabolic activity and with receptor-mediated transport of lysosomal enzymes.