The production of hydrogen peroxide is not a common mechanism by which olive oil phenols induce apoptosis on HL60 cells

We have recently demonstrated that hydroxytyrosol (3,4-DHPEA), the most representative olive oil phenol, induces apoptosis on HL60 cells through the production of considerable amount of extracellular hydrogen peroxide (H2O2). The aims of the present investigation were first to assess the ability of different phenolic compounds to both produce extracellular H2O2 and induce apoptosis on HL60 cells, and second to elucidate whether the pro-apoptotic activity was mediated by the production of H2O2 in the cell culture medium. Based on the results phenols can be classified as follows: (1) those which were not able to induce both apoptosis and H2O2 accumulation (tyrosol, homovanillic alcohol and protocatechuic, o-coumaric, vanillic, homovanillic, ferulic and syringic acids); (2) those which showed a pro-apoptotic activity mediated, at least in part, by the production of H2O2, as evidenced by the ability of catalase to inhibit apoptosis (3,4-DHPEA, dopamine, 3,4-dihydroxyphenylacetic, 3,4-dihydroxy-hydrocinnamic, caffeic and gallic acids); and (3) those which induced apoptosis without the involvement of H2O2 (the secoiridoid derivatives of both hydroxytyrosol and tyrosol). Oleuropein showed a peculiar behaviour since, and although it caused an abundant production of H2O2 in the cell culture medium, it exerted a weak pro-apoptotic effect. From these results we may conclude that the cathecol moiety of the phenol molecule is necessary for the H2O2 producing activity, and that the 3,4-DHPEA metabolism to homovanillic alcohol and homovanillic acid may significantly reduce its pro-apoptotic potential. The real in vivo meaning of the phenol-induced H2O2 production remains to be investigated.