APOPTOSIS INDUCED BY CALCITRIOL AND DL-BUTHIONINE-S,R-SULFOXIMINE IN BREAST CANCER CELLS

BOHL L, LIAUDAT C, MARCHIONATTI A, PICOTTO G, RODRÍGUEZ V, NARVÁEZ C, WELSH J, TOLOSA DE TALAMONI N.

Carlos Paz, Córdoba

Congreso; XLIV Reunión Anual - Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2008

SAIB

Breast cancer is one of the most frequent neoplasias. Calcitriol diminishes  cancer risk and constitutes an alternative therapy to the usual with antiestrogens. The aim of the present work was to study the molecular basis of the anticancer effect of calcitriol in combination with DL-buthionine-S,R-sulfoximine (BSO), a glutathione (GSH) depleting drug, in order to potentiate the antiproliferative effect of the secosteroid on breast cancer cells (MCF-7). Cultured cells were treated for 96 hs with calcitriol (100 nM), BSO (20 µM), calcitriol + BSO or vehicle. Cell proliferation was evaluated by crystal violet staining while GSH content and the activity of the antioxidant enzymatic system, superoxide dismutase and catalase, by spectrophometry. Either calcitriol or BSO alone significantly reduced cell proliferation, being maximal with the combined treatment. Calcitriol induced reactive oxygen species (ROS) formation, which was potentiated by BSO. DNA fragmentation and citochrome c release were induced by the steroid and the combination. Total levels of GSH were decreased. The antioxidant enzymes were not altered by any treatment.  In conclusion, BSO potentiated growth inhibition of calcitriol on breast cancer cells by apoptotic mechanisms involving ROS production and mitochondrial disruption.