Antitumor Activity of Copper-Based Metallodrugs Against Murine Triple Negative Breast Cancer

SÓLIMO ALDANA; SANTA MARIA DE LA PARRA LUCÍA; LEÓN IGNACIO E.; CALLERO MARIANA

Mar del Plata

Congreso; LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2023

A range of metallodrugs is used to treat cancer, with cisplatin, carboplatin, and oxaliplatin being the most commonly administered. However, platinum toxicity and resistance to treatment have caused researchers to explore new compounds that may be effective in treating tumor growth. Copper-based metallodrugs have been found to possess promising anti-tumor and anti-metastatic properties for a variety of types of solid tumors. Our aim was to investigate the anti-tumor effect of two metallodrugs (1 and 2) on the mouse triple-negative breast cancer model 4T1. MTS assays were carried out to determine the IC50 values and assess cytotoxicity. The cells showed an IC50 value of 1.2 ± 0.2 µM for complex 1 and 1.1 ± 0.2 µM for complex 2. We used ethidium bromide and acridine orange staining to determine that both metallodrugs induced cytotoxicity through apoptosis. Following a 24-hour treatment of the cells with either drug, we conducted a clonogenic assay and noted a reduction in colony-forming capacity. Both compounds significantly reduced colony formation at even their lowest concentration (IC50/4) with respect to control cells (70 ± 9 % for 1 and 69 ± 11 % for 2, p˂0,05). We also evaluated copper-based metallodrugs modulation on cell migration in a wound-healing assay. Following a 24-hour treatment period, we observed that both compounds effectively decreased cell migration capacity in comparison to the control cells when administered at a concentration equal to their IC50/2 (54 ± 6 % for 1 and 48 ± 15 % for 2, p˂0,05). Overall, our findings demonstrate that both complexes possess anti-tumor effects on 4T1 cells. Further research into the mechanism of action of copper-based metallodrugs may yield potential alternatives for triple negative breast cancer treatments.