IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Synergistic apoptotic effect of 2´nitroflavone combined with safingol in murine mammary tumor cells
Autor/es:
JUAN MANUEL ANSELMI RELATS; JULIETA MARINO; MARIEL MARDER; LEONOR P ROGUIN; VIVIANA C. BLANK
Lugar:
virtual
Reunión:
Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2021; 2021
Institución organizadora:
SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)
Resumen:
In a previous work, we have demonstrated that the synthetic flavonoid 2´-nitroflavone (2NF) is a potent and selective antitumor agent in vitro and in vivo in a murine LM3 breast cancer model. Sphingosine kinase 1 (SphK1), a lipid kinase overexpressed in some mammary tumor cells, regulates the balance between proapoptotic ceramides and prosurvival sphingosine-1-phosphate (S1P). Furthermore, safingol, a competitive SphK1 inhibitor, prevents catabolism of ceramides, contributing to tumor cell death. It has been reported that certain flavonoids exert antitumor activity through an increment in ceramide levels. Thus, we explored the antiproliferative effect of the simultaneous incubation of 2´NF and safingol in LM3 cells and found that they synergistically inhibited cell proliferation. Based on these results, we studied the apoptotic effect of 2NF in combination with safingol. When we evaluated the expression of bax proapoptotic protein, results obtained by Western blot showed that each compound alone did not modify bax expression, but a fivefold increase was observed after cell incubation with both 2NF and safingol for 24 h (p