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

ANSELMI RELATS JUAN M; ROGUIN, L. P; CERCATO M; MARDER M; MARINO, V. J; BLANK VC

Mar del Plata

Congreso; Reunión Conjunta SAIC, SAB, AAFE, AACYTAL; 2023

SAIC, SAB, AAFE, AACYTAL

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