In vitro and in vivo evidence of the antineoplastic activity of quercetin against Kaposi’s sarcoma

Abstract

Quercetin (QUE) is a natural flavonoid known to exhibit anticancer properties. Kaposi’s sarcoma is a viral cancer caused by the human herpesvirus-8, which expresses a constitutively activated G protein-coupled receptor (vGPCR) during its lytic phase, able to induce oncogenic modifications that lead to tumor development. The goal of this work was to explore the antineoplastic effect of QUE in an in vitro and in vivo model of Kaposi’s sarcoma. Firstly, the antiproliferative effect of QUE was determined by crystal violet technique at different concentrations of QUE (1 - 100 µM) or vehicle (DMSO) for 48 h in endothelial cells stably expressing the vGPCR (vGPCR cells), with an IC50 of 30.078 µM. In addition, a significant decrease in cell viability was observed by neutral red staining (QUE 30 - 100 µM, p < 0.05). At a molecular level, F-actin stained with phalloidin showed disorganized actin filaments in the presence of QUE (30 µM), resembling an apoptotic event. Then, apoptosis induced by QUE (30 µM, 24 h) was revealed by annexin V/PI analysis (p < 0.01) and caspase-3 activity (p < 0.001). Secondly, tumors from vGPCR cells were induced in nude mice. After 15 days of tumor development, mice were treated with QUE (50 or 100 mg/kg/d) or PBS (as control) administered by IP injection three times a week for 30 days. The results showed that tumor progression was retarded in mice treated with QUE (100 mg/kg/d) compared to control (p < 0.001); whereas tumor weight was reduced by QUE (50 or 100 mg/kg/d) at the end of the test (p < 0.05 and p < 0.01, respectively). Neither kidney nor liver damage was observed by analyzing biochemical parameters in serum. In conclusion, this study suggests that QUE exhibits antineoplastic activity in both, an in vitro and in vivo model of Kaposi’s sarcoma.