Antiproliferative effect of glibenclamide in MDA-MB-231 cell line

M. NUÑEZ; G. MARTÍN; V. MEDINA; N. MOHAMAD; G. CRICCO; A. GUTIÉRREZ; E. RIVERA; R BERGOC

Rosario, Argentina

Congreso; XLII Reunión Anual de la Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular; 2006

Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular

Glibenclamide (Gli) is a sulphonylurea widely used for treatment of non-insulin-dependent diabetes mellitus, and signaled as antitumoral in several cell lines. We previously demonstrated the antitumoral effect of Gli on mammary tumors induced in rats. The aim of this work was to study the in vitro effect of Gli alone or combined with tamoxifen (Tam) on MDA-MB-231 breast cancer cells. Cell growth was determined using the clonogenic assay and results indicate that Gli inhibited it in a dose dependent manner (IC50=25 ìM). Gli also produced a significant cell-cycle arrest in G0/G1 phase ( 89% vs. 50% in controls), analyzed by flow cytometry. In agreement, the doubling time showed a significant increase after Gli treatment (34.6 h vs. 24.9h in controls) and PCNA expression decreased significantly (66% vs. 100%), evaluated by flow cytometry. However, neither differentiation nor apoptosis was detected by nile red staining and Annexin V, respectively. Furthermore, the cell proliferation inhibition upon Gli addition was reverted after treatment removal. The combination of Gli plus Tam (0.1, 1, and 5 ìM) produced similar results to Gli alone. We conclude that Gli inhibits the G1/S phase progression without inducing apoptosis suggesting a novel use of Gli as an alternative drug to treat breast cancer however, further studies are necessary to elucidate the mechanism involved in growth arrest. POSTER