Anticancer mechanisms of calcitriol and menadione on breast cancer cells

RODRÍGUEZ V; GUIZZARDI S; BOHL L; PICOTTO G; TOLOSA DE TALAMONI N

Mar del Plata

Congreso; Reunión Anual SAIC-SAI-SAFIS; 2018

Calcitriol (D), the active form derived from vitamin D3, presents antineoplastic properties in several types of cancer. However, its use as an antitumoral agent may promote secondary effects. We have demonstrated that menadione (MEN) potentiates the antiproliferative effect of D on breast cancer MCF-7 cells, at least in part, by cell cycle alteration and increasing intracellular calcium and ROS and NOS production, although the mechanisms are still under study. Our working hypothesis was that the combined treatment of D and MEN could increase the antitumoral effect of D, mainly via activation of autophagy and reduction of the migration of the MCF-7 cells. The aim of the present study was to investigate further the mechanisms involved in the antiproliferative action of the combined treatment. MCF-7 cells were treated with 100 nM D, 10 µM MEN, both or vehicle (96 h). Gene and protein expression of PMCA1b were measured by qRT-PCR and western blot, respectively. Induction of autophagy was evaluated through detection of acidic vesicular organelles (AVOs) by fluorescence microscopy and the protein expression of LC3II by western blot. Cell migration was estimated by the wound healing assay. Statistical analyses were performed by ANOVA/Bonferroni. Differences were considered significant at p