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

**Authors:** Thayná Oliveira da Silva, Luís Gustavo Ramos de Moraes Calheiros, Felipe Barbosa, Fernanda Bueno Morrone, Liliana Rockenbach, Patrícia de Faria Lainetti, Antonio Fernando Leis Filho, Márcio de Carvalho, Carlos Eduardo Fonseca-Alves, Renée Laufer Amorim

PMC · DOI: 10.3390/ani15111589 · 2025-05-29

## TL;DR

This study shows that curcumin and turmeric may help fight bladder cancer in dogs and humans by reducing cancer cell growth and migration.

## Contribution

The study explores curcumin and D6 turmeric as potential adjuvants for canine and human bladder cancer treatment.

## Key findings

- Curcumin reduced cancer cell viability and migration in both canine and human cell lines.
- Mitoxantrone hydrochloride showed strong cytotoxic effects, especially in canine cells.
- Curcumin induced apoptosis and modulated genes related to cancer progression.

## Abstract

Bladder cancer is a challenging disease in both humans and dogs, and current treatments such as surgery and chemotherapy often yield limited success. Because dogs naturally develop this cancer and share many clinical and biological features with humans, they are valuable models for investigating new therapies. In this study, we tested curcumin—a natural compound derived from turmeric—alongside a chemotherapeutic agent on bladder cancer cell lines from both species. Our results demonstrated that curcumin decreased cancer cell viability, reduced migration, and increased apoptosis. The chemotherapeutic drug showed pronounced cytotoxic effects in canine cells. These findings support the potential use of curcumin as an adjuvant to conventional therapies, possibly improving outcomes in dogs with bladder cancer. Further research is needed to better understand curcumin’s mechanisms and safety profile in vivo. This study lays the groundwork for the future development of novel and less toxic therapeutic strategies that could benefit both veterinary and human medicine.

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 (β-catenin, β1-integrin, CDH1, MMP-2, MMP-9, and TIMP-2) 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.

## Linked entities

- **Genes:** ctnnb1.S (catenin beta 1 S homeolog) [NCBI Gene 380441], CDH1 (cadherin 1) [NCBI Gene 999], MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313], MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318], TIMP2 (TIMP metallopeptidase inhibitor 2) [NCBI Gene 7077]
- **Chemicals:** curcumin (PubChem CID 969516), mitoxantrone hydrochloride (PubChem CID 51082)
- **Diseases:** bladder cancer (MONDO:0004986), bladder urothelial carcinoma (MONDO:0005611)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** MMP9 (matrix metallopeptidase 9) [NCBI Gene 403885], CTNNB1 (catenin beta 1) [NCBI Gene 477032], TIMP2 (TIMP metallopeptidase inhibitor 2) [NCBI Gene 403633], MMP2 (matrix metallopeptidase 2) [NCBI Gene 403733] {aka MMP-2}, CDH1 (cadherin 1) [NCBI Gene 442858] {aka Cadherin-1, Uvomorulin}
- **Diseases:** Bladder urothelial carcinoma (MESH:D001749), inflammatory (MESH:D007249), malignancy (MESH:D009369), cytotoxicity (MESH:D064420), UC (MESH:D014523)
- **Chemicals:** MTT (MESH:C070243), Mitoxantrone (MESH:D008942), D6 Turmeric (-), Curcumin (MESH:D003474)
- **Species:** Homo sapiens (human, species) [taxon 9606], Canis lupus familiaris (dog, subspecies) [taxon 9615], Curcuma longa (turmeric, species) [taxon 136217]

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12153849/full.md

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Source: https://tomesphere.com/paper/PMC12153849