COMBINED TREATMENT OF MENADIONE PLUS CALCITRIOL ON CACO-2 CANCER CELLS: ANTIPROLIFERATIVE EFFECTS

TOLOSA DE TALAMONI N; COLLIN A; KOHAN R; PICOTTO G

Mar del Plata

Congreso; Congreso de SAIC; 2019

Colorectalcancer (CRC) is the third most frequent and the fourth leading cause ofcancer-associated mortalities worldwide. Effective targeted therapies based on the currentknowledge of CRC are essential to achieve a successful treatment of thispathology.  We have previously reported thatoxidant drugs as menadione (MEN) increased tumour cell sensibility. Calcitriol(D) has well known antineoplastic actions on different tumor cells. However,the doses employed to reach this effect invivo have undesirable hypercalcemic consequences. The aim ofthis study was to evaluate the effects of a combined MENand D therapy on the viabilityof Caco-2 colon cancer cells and to study reactive oxygen species as possibleinductors of oxidative stress (OS). Cells were treated with MEN, D, both orvehicle (ethanol). Crystal violet staining and microscopyevaluated antiproliferative effects. Cell migration wasestimated by wound healing assay. Superoxide anion content, catalase(CAT) activity and cellular adhesion were also determined. One way ANOVA andBonferroni as a post-hoc test were used as statistical methods.  MEN and D inhibited Caco-2 growth in a timeand dose-dependent manner. The antiproliferative effect began at48h being higher at 96h. The selected concentration was 20µMMEN/200nM D. The combined treatment caused a dramatic reduction ofviability (>80%) and a complete inhibition of cell migration. Morphologicalnuclear changes resulted compatible with cell death. Changes in cell adhesion werenot observed. Superoxide anion content increased by the combined treatment concomitantwith modifications in CAT activity. The antiproliferative effect of thecombination was partially rescued exposing cells to the flavonoid naringin, anatural antioxidant. In conclusion, D enhances the antiproliferative effect ofMEN on Caco-2 cells probably via the induction of OS. The study of thisdrug combination will continue in order to analyse future therapeuticsapplications.