Antitumor Effect of Curcumin, D6 Turmeric, and Hydrochloride Mitoxantrone on Canine and Human Urothelial Cancer Cells

Abstract

Bladder urothelial carcinoma (UC) is an aggressive malignancy in both humans and dogs, with limited treatment options. Owing to their biological and environmental similarities with humans, dogs serve as a valuable model for UC research. Standard treatments, including surgery, chemotherapy, and anti-inflammatory agents, have shown limited efficacy. Curcumin, a bioactive compound derived from turmeric, has demonstrated anticancer properties, but its potential in canine UC remains poorly understood. In this study, we evaluated the effects of curcumin, D6 turmeric, and mitoxantrone hydrochloride on canine and human UC cell lines. Cell viability was assessed via the MTT assay, apoptosis via flow cytometry, and gene expression (<i>β-catenin</i>, <i>β1-integrin</i>, <i>CDH1</i>, <i>MMP-2</i>, <i>MMP-9</i>, and <i>TIMP-2</i>) via quantitative PCR. Migration capacity was analyzed using a Transwell assay. Curcumin and D6 turmeric reduced cell viability and migration, while mitoxantrone hydrochloride exhibited strong cytotoxicity, especially in canine cells. Curcumin also induced apoptosis and modulated genes involved in epithelial-mesenchymal transition and invasion. The interindividual differences in response suggest underlying genetic variability and highlight the need for personalized therapeutic approaches. These findings suggest that curcumin and D6 turmeric hold promise as complementary therapies for canine UC, justifying further in vivo investigations.