IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The flavonoid 2?nitroflavone inhibits proliferation, survival and migration of human triple-negative breast cancer cells
Autor/es:
VACHETTA VS ; TRONCOSO MF; ELOLA MT; MARDER M
Lugar:
Rosario
Reunión:
Congreso; Reunión Anual de la Sociedad Argentina de Fisiología; 2019
Institución organizadora:
Sociedad Argentina de Fisiología
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 previously described 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-like TNBC subtype), MDA-MB-231 (Claudine-low TNBC subtype) and BT-549 (Claudine-low TNBC subtype) cell viability (MTT assay). The half maximal inhibitory concentrations (IC50 mean, 95% confidence interval) were 3.3 (2.7-4.2), 2.1 (0.6-7.0) and 2.9 (2.4-3.5) µM at 96 h 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 inhibits proliferation, 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.