BIOLOGICAL IMPACT OF MAGNESIUM(II)-LUTEOLIN COMPLEX: ANTICANCER AND ANTIMETASTATIC ACTIVITY

NASO LUCIANA; BRAIAN GUTIERREZ; SABRINA DI MARZIO; JULIANA PARENTE; ANGELA CANDREVA; CECILIA ALVAREZ

Otro; SAIC; 2023

Introduction Cervical cancer is the fourth most common malignancy in women worldwide and the second-most prevalent gynecological cancer. Although standard treatments are beneficial for early-stage cervical cancer, their efficacy for locally advanced is restricted due to significant side effects, drug resistance, and metastases. In this context, natural products, such as flavonoids, can be considered as a potentially effective replacement for chemotherapy drugs.Objective The main goal was to evaluate the anticancer and antimetastatic capacity of Mglut, a newly synthesized and characterized Magnesium(II)-luteolin complex. The basis of our hypothesis is that flavonoids structurally modified by coordination show improved biological properties.Methods The MTT test was performed to assess the impact of the compounds on HeLa cell viability. Intracellular reactive oxygen species ROS levels (CM-H2DCFDA probe), mitochondrial membrane potential (PMM) (DIOC6 probe) were studied to determine the probable mechanism of action. The induction of apoptosis and morphological changes were measured with flow cytometry (Annexin V-IP) and staining with crystal violet, respectively. The inhibition of cell invasion, migration, and adhesion was also investigated.Results Lut and Mglut inhibited the growth of HeLa cells in a dose-dependent manner being its IC50 values >100 and 70.8 µM, respectively, and both reduced slightly the HaCat cells viability. The HeLa cells incubated with 100 µM Mglut displayed morphological changes typical with apoptosis, such as cellular shrinkage and disruption. The free ligand and complex increased ROS levels while decreasing PMM levels in dose-dependent ways. Likewise, lut an Mglut induced apoptosis and necrosis. At non-cytotoxic concentrations, both compounds decreased cell migration (82.8 and 62.1%), invasion (84.3 and 60.7%) and collagen type I adhesion (6.8 and 25.9 %).Conclusion Antitumor and antimetastatic activity of luteolin enhance upon coordination.