ANTIMETASTATIC AND CYTOTOXIC PROPERTIES OF A NEW COMPOUND BASED ON SILIBININ AND MAGNESIUM(II) CATION

JUAN JOSÉ MARTÍNEZ MEDINA; JAVIER RODRIGUEZ; LUCIANA NASO

Mar del Plata

Otro; LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC) LXX REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI) & 3ER CONGRESO FRANCO-ARGENTINO DE INMUNOLOGÍA (FAIC) REUNIÓN ANUAL 2022 DE LA SOCIEDAD ARGENTINA DE FISIOLOGÍA; 2022

Objective: On the basis that metal-chelated flavonoids show better biological effects than flavonoids, we have synthesized and characterized a new coordination compound between silibinin and magnesium(II) cation (Mgsil). The anticancer and antimetastatic activity on the HeLa cell line was determined and coupled with a safety evaluation. Methods: Mgsil has been characterized by spectroscopy techniques. The effects of the compounds on the cell viability were measured by MTT assay. To evaluate the probable mechanism of action, morphological changes, intracellular reactive oxygen species ROS content (using CM-H2DCFDA probe), and mitochondrial membrane potential (MMP) (using DIOC6 probe) were used. The effect of the compounds, at non-cytotoxic concentrations, on adhesion, migration, and invasion was investigated. The safety profile of Mgsil was assessed in terms of mutagenicity (Ames test) and acute toxicity (Artemia salina test). Results: The proposed structure for the compound is [Mg(sil)(OH2)2]Cl.3H2O. A significant decrease (ca. 70 %) in HeLa cell viability was observed at the concentration of 100 µM of Mgsil after 24 h treatment. Our results were consistent with morphological changes noted: cell shrinkage and nuclear condensation. Silibinin and Mg(II) cation did not induce cell death at tested concentrations. Mgsil was not toxic for HaCat cells (inhibiting 18 % cell viability at 100 μM), showing its specific toxicity against the cervical cancer cells. Besides, it has not mutagenic behavior on Salmonella typhimurium (TA98 and TA100) and no toxicity on brine shrimp at this concentration. The complex produced an increment in ROS levels and a decrease of MMP in a dose-dependent manner (ca. 200 and 30 % at 100 μM, respectively) compared to the untreated cells. Mgsil suppressed cell migration, adhesion, and invasion (at 10 µM). Conclusion: Mgsil has an adequate safety profile and is capable of inducing HeLa cell death and of reducing, in vitro, cervical cancer metastasis