Synergistic in vivo antitumor effect of 2’-nitroflavone and safingol combination

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

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

The sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)axis has been widely studied in cancer research due to its role inmodulating sphingolipid metabolism, which determines cell survivalor death. In this sense, the development of SphK1 inhibitors hasemerged as a promising strategy due to their ability to increasepro-apoptotic ceramide and decrease oncogenic S1P levels. Inaddition, it has been reported that certain flavonoids exert antitumoractivity through an increase in ceramide levels. Previously, wedemonstrated that the synthetic flavonoid, 2’-nitroflavone (2NF), andthe SphK1 inhibitor, safingol, synergistically inhibited cell proliferationand induced apoptosis in vitro in breast tumor cells. In this work,we studied the effects of the 2NF and safingol combination in anin vivo syngeneic LM3 breast cancer murine model. Animals weretreated with either vehicle, 2NF (0.7 mg/kg), safingol (0.5 mg/kg) orthe combination of these drugs three times per week for two weeks.Results showed that the administration of 2NF reduced tumor volumeby 38% (p