Preclinical study of curcumin with doxorubicin in murine breast cancer cells

Keywords

breast cancer - curcumin - doxorubicin - 4T1 cells

Introduction: Breast cancer is highly heterogeneous and includes different phenotypic and morphological types that define therapeutic conduct. In this meaning, murine mammary carcinoma cells models are fundamental to comprehend tumor growth, as the therapeutic response to new anticancer drugs that can be used in future treatments.

Objectives: The aim of this study was to investigate the effect of curcumin, a polyphenol found in the Curcuma longa L., in association with Doxorubicin, a traditional chemotherapic in murine triple-negative breast cancer cell line 4T1.

Material and Methods: The viability of 4T1 cells was evaluated using the MTT assay. The phases of the cell cycle were analyzed in flow cytometry after labeling with RNAse-propidium iodide (PI). The morphological characteristics were analyzed with Giemsa stain. The characterization of cell death was investigated by labeling with PI and Annexin-V. The mitochondrial membrane potential (ΔΨm) and the detection of reactive oxygen species (ROS) were analyzed by flow cytometry after labeled the cells with JC-1 and DCFDA, respectively.

Results: Curcumin and doxorubicin had a cytotoxic effect in 4T1 cells, after 24 and 48 hours of treatment, with IC50 values of 120.5 µM and 38.75 µM for curcumin and 8.05 µM and 5.83 µM for doxorubicin, respectively. The association of 18.99 µM curcumin with 0.36 µM of doxorubicin showed synergistic effect in the inhibition of 4T1 cell growth after 48 hours of treatment. Besides, this association decreases 16-fold the concentrations of doxorubicin. Morphological analyses of 4T1 cells demonstrated alterations in the presence of curcumin and doxorubicin alone or in association. Curcumin decreases ROS production and alters the ∆ᴪM. Curcumin decreases G0/G1 phases, and the association of curcumin and doxorubicin decreases G0/G1 phases and increases the S and G2/M phases. The association increased the number of PI-labeled cells, which characterizes death by necrosis. In addition, in vivo murine trials are ongoing.

Conclusion: Curcumin treatment demonstrated a significant effect alone or in combination with doxorubicin in vitro, suggesting a new potential therapeutic approach that can reduces the doses of isolated traditional compounds and minimize adverse effects of the treatments.

Corresponding author: Gustavo de Souza Gomes (e-mail: [e-mail]).

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
06 May 2025