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

Abstract 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 (H 2 O 2 ). The aims of the present investigation were first to assess the ability of different phenolic compounds to both produce extracellular H 2 O 2 and induce apoptosis on HL60 cells, and second to elucidate whether the pro-apoptotic activity was mediated by the production of H 2 O 2 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 H 2 O 2 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 H 2 O 2 , 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 H 2 O 2 (the secoiridoid derivatives of both hydroxytyrosol and tyrosol). Oleuropein showed a peculiar behaviour since, and although it caused an abundant production of H 2 O 2 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 H 2 O 2 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 H 2 O 2 production remains to be investigated.