Immunomodulatory and cytotoxic activities of euphol.

ABSTRACT

AIMS: This study evaluated the effect of euphol isolated from Euphorbia umbellata (Pax) Bruyns latex on the activation of complement pathways (classical (CP), alternative (AP) and lectin (LP)), neutrophil chemotaxis, cytotoxic activity, cell morphology and death in HRT-18 and 3T3 cells lines. MAIN METHODS: CP and AP were assessed using hemolytic assays and ELISA for LP; neutrophil chemotaxis was performed using Boyden's chamber; cytotoxicity was evaluated by neutral red methodology and characteristics of cell death were assessed by cell morphology with hematological staining. KEY FINDINGS: Although euphol increased CP activation (38% at a concentration of 976.1 µM), an inhibitory effect on AP, LP (31% and 32% reduction in the concentration of 976.1 µM) and neutrophil chemotaxis (inhibit 84% of neutrophil migration at a concentration 292.9 µM) was observed. In addiction euphol was able to induce significant cell death in a time-dependent manner, presenting an IC50 of 70.8 µM and 39.2 µM for HRT-18 and 3T3 cell lines respectively and it was also observed apoptotic characteristics as cellular rounding, chromatin condensation and blebs formation for both cell lines. SIGNIFICANCE: Euphol has a potential use for the treatment of complement-related inflammatory diseases due to its ability to downregulate inflammation. On the other hand, the controlled activation of CP can contribute to complement-dependent cytotoxicity in the context of monoclonal antibody-based cancer treatment.