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Inhibition of xCT using sulfasalazine, which is used for inflammatory bowel disease in dogs, can disrupt the redox balance of tumor cells by suppressing GSH synthesis 22,23 GSH deprivation using sulfasalazine induces free radical accumulation and tumor cell death via ferroptosis and apoptosis 24 Moreover, sulfasalazine targets tumor cells with high expression levels of CSC markers, such as CD133 or CD44v, 25,26 and prolongs the survival of rat brain tumor models by inducing CSC death 27 A clinical study of gastric tumors showed that sulfasalazine can reduce the population of CSCs in gastric tumor tissues 28 Furthermore, in a study of canine liver tumors, the xCT of canine CSCs was upregulated and sulfasalazine decreased the sphere-forming capacity of the cells 29 Our previous report also demonstrated that visualized canine tumor cells with low proteasome activity have upregulated CD133 and possess CSC-like properties 5 These findings suggest that sulfasalazine may target canine tumor cells with low proteasome activity, making it a promising radiosensitizer candidate for eliminating canine CSCs

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H., Wijaya, S