Effect of antioxidant properties of CAPE derivatives on anticancer activity of Cold Plasma

Introduction: Caffeic acid phenethyl ester (CAPE), a natural polyphenolic compound coming from bee propolis, is known to have many biological activities including anti-tumoral selective effects. Cold Atmospheric Plasmas (CAP) therapeutic potential is largely based on the generation of reactive oxygen species (ROS). Materials & Methods: Two different novel series of CAPE derivatives were designed, synthesized and administered in different concentrations to human sarcoma cell model (MG63) alone or in combination with direct CAP treatment /atmospheric pressure plasma jet, APPJ, 1 L/min halium flow rate). Results: Even though the compounds MB10 and MB14 had very promising IC50 values, 26 uM and 30 uM respectively, they surprisingly proved to revert the cytotoxicity exerted by CAP in MG63 cells. In addition, their administration at concentrations higher than IC50 values (40 and 80 uM) resulted in a decrease of the concentration of H2O2 generated by CAP. On the other hand, a synergic cytotoxic effect towards MG63 was observed when MB14 was used at concentrations lower than its IC50, in combination with CAP. Conclusion: These results suggest to carefully consider the antioxidant effects of polyphenols when combined with CAP, and underline the key role of drug dose in anticancer therapy.