MECHANISM OF 2´-NITROFLAVONE AND SAFINGOL ANTITUMOR SYNERGISTIC COMBINATION IN MAMMARY CANCER CELLS

JUAN MANUEL ANSELMI RELATS ; LEONOR ROGUIN; MARIEL MARDER; JULIETA MARINO; VIVIANA BLANK

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

Sphingosine kinase 1 (SphK1), a lipid kinase overexpressed in somemammary tumor cells, regulates the balance between proapoptoticceramides and prosurvival sphingosine-1-phosphate. Furthermore,SphK1 inhibitors prevent catabolism of ceramides, contributing totumor cell death. It has been reported that certain flavonoids exertantitumor activity through an increment in ceramide levels. Previously,we demonstrated that the synthetic flavonoid 2´-nitroflavone(2NF) and the SphK1 inhibitor safingol synergistically inhibited cellproliferation and induced apoptosis in LM3 murine mammary tumorcells. In this work, we examined the modulation of JNK and ERK1/2 MAPK transduction pathways. Results showed that after 1h ofincubation with both compounds, the levels of p-JNK and p-ERK1/2MAPKs were significantly increased (2,3 ± 0,3 fold, p