Cytotoxicity of propolis nanopreparations in cancer cell monolayers: multimode of action including apoptotsis and nitric oxide production

Natural products are invaluable resource of anticancer drug discovery. They generally viewed as safe but weak, within the framework of nanotechnology, they can serve as template for potent anticancer drugs. We first evaluated the cytotoxic activity of different propolis extracts (water, 70% ethanol, absolute ethanol and hexane) in many cancer cell lines, then the solid nanoparticles from the organic solvent extracts were prepared and their cytotoxicity was evaluated as well. Finally, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes were prepared from the most cytotoxic organic solvent extract and their cytotoxicity was also evaluated. All results collectively showed that hexane extract and its solid nanoparticles as well as its liposomal form exhibited high cytotoxic activity. DPPC/DOPC-hexane extract cytotoxicity selectively depends on the cell line and DOPC liposomal form was characterized by reduced IC50 compared with the other preparations/extracts, the average IC50 value is 165.8 ± 3 µg/ml. The antiproliferative activity of propolis was associated to multiple modes of actions including apoptosis and nitric oxide production and as indicated by the HPLC and FTIR results, it is functioning in many propolis ingredients rather than a single component and influenced by the presence of more lipophilic components within the extract and not by the extract mass yield. These results may have an impact on the multidrug resistivity issue.