IQUIR   05412
INSTITUTO DE QUIMICA ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Proliferation study on 4T1 cells treated with anthelmintic cyclodextrin complexes as repositioning compounds
Autor/es:
PRIOTTI, J.; MENACHO-MÁRQUEZ, M.; GARCÍA, A.; LAMAS, MC.; BAGLIONI, MV.; LEONARDI, D.
Lugar:
Rosario
Reunión:
Congreso; 4ta. Reunión Internacional de Ciencias Farmacéuticas; 2016
Resumen:
Benzimidazole compounds as albendazole (ABZ), mebendazole (MBZ) and ricobendazole (RBZ) are extensively used in anthelmintic treatment. They can inhibit microtubule polymerization blocking mitosis and resulting in cell death. Nevertheless, these compounds present very low aqueous solubility and erratic bioavailability. Therefore, the use of cyclodextrins is a promising choice to enhance their solubility and bioavailability. Otherwise, pharmaceutical research is focusing the attention on developing more suitable dosage forms, improving the efficacy and avoiding adverse effects. There are many approaches to fulfill this aim, and one of these issues is the re-use of existing drugs for new indications. Drug repurposing refers to the use of compounds, which were not developed for cancer treatment but showed an antitumor effect. The aim of this research work was to evaluate the antitumor activity of benzimidazole compounds, and the β-cyclodextrin inclusion complexes, and the combination with cytotoxic drugs on breast cancer. In order to assay in vitro 4T1 cell proliferation inhibition, 2x103cells/well were plated on 96-well culture plates and incubated 48 h at 37°C and 5% CO2. The number of living cells was estimated by tetrazolium salt reduction method (WST-1). ABZ, MBZ (0.1-5 µM) and RBZ (1-100 µM) and the inclusion complexes with β-cyclodextrin derivatives were tested and combined with doxorrubicin (Doxo, 0.025 µM) and 5-fluorouracil (5-FU, 0.2 µM). ABZ + 5-FU treatment showed higher cell proliferation inhibition than 5-FU (p