CALCITRIOL AND DL-BUTHIONINE-S,R-SULFOXIMINE REDUCE PROLIFERATION AND INDUCE APOPTOSIS IN BREAST CANCER CELLS

C. LIAUDAT, L. BOHL, RODRÍGUEZ V, PICOTTO G, TOLOSA DE TALAMONI N

Santiago de Chile, Chile

Otro; Free Radicals and Antioxidants. VI Meeting of SFRBM South American Group; 2009

Calcitriol constitutes an alternative therapy of breast cancer to the usual with antiestrogens. Calcitriol can be administered to reduce cancer growth, but its use is limited due to the secondary effects such as hipercalcemia. To reduce its undesirable side effects, DL-buthionine-S,R-sulfoximine (BSO), a glutathione (GSH) depleting drug, might be used in combination with calcitriol. The aim of the present work was to study the molecular basis of the anticancer effect of calcitriol in combination with BSO 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) and BSO (20 µM), alone or in combination, or vehicle. Cell proliferation was evaluated by crystal violet staining while GSH content by spectrophometry. Either calcitriol or BSO alone significantly reduced cell proliferation, being maximal with the combined treatment. The reactive oxygen species (ROS), determined by flow citometry, were increased by calcitriol, effect that was potentiated by BSO. Total levels of GSH were decreased. DNA fragmentation and citochrome c release from mitochondria were highly induced by the steroid and the combined treatment. In conclusion, BSO potentiated growth inhibition of calcitriol on breast cancer cells by apoptotic mechanisms involving ROS production and mitochondrial disruption.