IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The flavonoid 2nitroflavone inhibits survival and migration of human triple-negative breast cancer cells. inhibits proliferation, survival and migration of human triple-negative breast cancer cells
Autor/es:
MARDER, MARIEL; VACHETTA, VANINA; TRONCOSO, MARÍA F.; ELOLA, MARÍA TERESA
Lugar:
ROSARIO, PROVINCIA DE SANTA FE
Reunión:
Congreso; REUNION ANUAL DE LA SOCIEDAD ARGENTINA DE FISIOLOGIA 2019; 2019
Institución organizadora:
SOCIEDAD ARGENTINA DE FISIOLOGIA
Resumen:
Triple-negative breast cancer (TNBC) is one the most aggressive subtype of mammary tumor.As TNBC cells lack estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2), neither endocrine nor anti-HER2 molecular targeting therapy work. Flavonoids are a group of polyphenolic compounds considered potential chemopreventive candidates for cancer treatment.We previouslydescribed that the synthetic flavonoid 2?nitroflavone (2?NF) induces LM3 murine breast cancer cell apoptosis and acts as an anti-tumor agent in vivo. Our aim was to evaluate 2?NF effect on human TNBC cell proliferation, survival and migration. 2?NF exerted a dose- and time-dependent inhibitory effect on MDA-MB-468 (Basal-likeTNBC subtype), MDA-MB-231 (Claudine-low TNBC subtype) and BT-549 (Claudine-low TNBC subtype) cellviability (MTT assay). The half maximal inhibitory concentrations (IC50 mean, 95% confidence interval) were3.3(2.7-4.2),2.1 (0.6-7.0)and 2.9(2.4-3.5) µM at 96h for MDA-MB-468,MDA-MB-231 and BT-549 cells, respectively. Significant inhibitory effects on colony formation were observed in 2?NF-treated TNBC cells (Clonogenic survival assay). Colony formation at 7 days was:74±9, 54±6% for MDA-MB-468 cells;46±19,12±7%for MDA-MB-231 cells;79±19,29±10% for BT-549 cells versus the corresponding control cells (100%)after 3-day treatment with 1.2 and 2.5 µM 2´NF, respectively. Similar results were founded after 6-day treatment.At conditions which do not affect cell viability, 2?NF inhibited claudine-low TNBC cell migration(Wound-healing assay) in a dose-dependent manner. In the presence of 1.2 and 2.5 µM 2?NF, cell migration at 48 h significantly decreased versus vehicle (100%):80.0±4.5 and 27.4±0.1% for MDA-MB-231 cells,65.5±4.1 and 52.3±10.2% for BT-549 cells, respectively.Basal-like TNBC MDA-MB-468 cell migration was not affected by 2?NF at concentrations 0.02-0.2 µM, while higher doses inhibited cell proliferation.In conclusion, 2?NF inhibitsproliferation, viability and survival of MDA-MB-468, MDA-MB-231 and BT-549 cells, and cell migration in claudine-low TNBC cells. Thus, we propose 2?NF as a novel potential candidate for TNBC therapy.