Aloysia Polystachya anti-cancer action in colorectal cáncer

Abstract

Previously we have shown that extracts from the plant Aloysiapolystachya (AP) have a cytotoxic action in colorectal cancer cellsbut its lower in non-tumoral cells. The coactivator of nuclear receptorsRAC3 is overexpressed in several types of cancer, like colorectalcancer, but its expression is low in non-tumoral cells. Thismolecule is co-activator of the Aryl Hydrocarbon Receptor (AHR),a modulator of intestinal balance, whose expression is increased intumors. The aim of this work was to investigate the molecular mechanismsof AP cytotoxic action and its possible components involvedwith this effect in colorectal cancer. Since RAC3 expression and APcytotoxicity are low in non-tumoral cells, and RAC3 is coactivator ofAHR and NF-ĸB, we first decided to analyze if these molecules wereinvolved in AP effect. When colorectal cancer HCT116 cells wereincubated with AP extract we found by immunofluorescence assaythat the nuclear translocation of these molecules were increasedand that AHR and RAC3 co-localized in these cells. Then, we comparedthe biological activity of two AP plants grown in different partsof Argentina and found that both were capable to induce cytotoxicityin HCT116 cells (1:2 dilution % cytotoxicity: Buenos Aires 46%,p<0.05; Misiones 53%, p<0.01). We also performed cytotoxicityassays of AP essential oil, which is more pure and concentratedthan the extract, and observed that it had a cytotoxic action in thesecells, maintaining the biological activity of the extract (98% cytotoxicitywith 1:2 dilution, p<0.05). Finally, we determined the cytotoxicactivity of different fractions of AP extract and found that both hydrophobicand hydrophilic components of AP had an anti-tumor activityin HCT116 cells. From these results we conclude that AP extractcytotoxic effect over colorectal cancer cells could involve AHR andRAC3 and could be through the combination of hydrophilic and hydrophobic components.