Melatonin enhances anti-tumoral effects of menadione on colon cáncer cells.

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

Congreso; Reunión conjunta de sociedades de biociencias; 2017

Coloncancer is one of the most important causes of death in entire world. Newpharmacological strategies are always needed, especially in resistant variantsof this pathology. We have previously reported that oxidant drugs such asmenadione (MEN) or D,L-buthionine-S,R-sulfoximine (BSO) increase tumour cellsensibility, due to their well known ability to reduce glutathione (GSH)content. Besides, melatonin (MEL), a hormone regulating circadian rhythms, hasantioxidant and antiapoptotic properties at low concentrations, while at highdoses it has been shown to inhibit the growth of tumor cells. The aim of thisstudy was to evaluate the the effects of MEN and MEL on the proliferation ofcolon cancer cells. Caco-2 cells (human colon adenocarcinoma)were treated with MEN, MEL, both or vehicle (ethanol). Cell proliferation wasevaluated by crystal violet staining. Superoxide anion, glutathione levels(GSH) and nitric oxide (NO) levels were measured by spectrophotometry. Nuclearmorphology was evaluated by Hoechst staining and cell migration by the woundhealing assay. Statistically analyses: one way ANOVAand Bonferroni as a post-hoc test. MEN and MEL inhibited Caco-2 growth and thiseffect was time and dose-dependent. Theantiproliferative effect began at 48 h being higher at 96 h. The concentration used for the next set of experiments was 20 µM and 750 µM for MEN and MEL, respectively. TotalGSH levels decreased at 6 h with MEN, which was blocked by MEL. Superoxideanion increased by MEN, and the NO production was increased by MEN, MEL and MEN+MEL. The combinedtreatment caused morphological nuclear changes, compatible with cell death.Cell migration was decreased by all treatments. In conclusion, MEL enhances theantiproliferative effect of MEN on Caco-2 cells mainly via nitrosative stress andarrest of cell migration. This combination might be useful as a tool forintestinal cancer therapy.