ABSTRACT The beneficial role of extra-virgin olive oil on human health was recently attributed to the presence of minor components, with a particular interest toward the phenolic compounds. The phenolic composition of olive oil is complex and includes hydroxytyrosol (3,4-dihydroxyphenylethanol: HT), tyrosol (hydroxyphenylethanol), the dialdehydic form of elenolic acid linked to hydroxytyrosol or tyrosol (oleocanthal), oleuropein aglycon and lignans. Olive oil phenols, in particular HT, have been deeply investigated in the last past years and it has been showed that this phenol may be involved in the prevention of chronic-degenerative disease, like cardiovascular diseases and cancer, through antioxidant mechanisms. However, the biological effects of olive oil polyphenols are not limited to the antioxidant property. Indeed, several researchers have recently demonstrated that olive oil polyphenols are also able to modulate both gene expression and different pathways involved in the regulation of many physiological and pathological conditions. In this field, we show our recent findings on the in vitro chemopreventive activities of HT. We have demonstrated that HT, at relatively high doses (100µM), is able to inhibit proliferation and to arrest cell cycle progression through the up-regulation of the cyclin dependent protein kinase inhibitors p21 and p27 on HL60 promyelocytic cell line. These effects were associated to the induction of differentiation and apoptosis. The initial stress signal responsible for these effects was the HT-induced extracellular production of H2O2. HT was also able to inhibit the proliferation of human tumour cells derived from colon, prostate and breast, indicating an important role in the prevention of the promotion phase of carcinogenesis. In addition, we have observed by the comet assay that HT, at lower doses (1-10µM), is able to inhibit the oxidative DNA damage in human leukocytes so suggesting a preventive mechanism in the initiation phase of carcinogenesis. These results have allowed us to highlight that HT is able to induce either pro-oxidant or anti-oxidant effects which are depend on exposition doses. Furthermore, we demonstrated that HT (50-100µM) was able to prevent LPS-mediated COX2 induction on human monocytes at both mRNA and protein levels. These effects were associated to a significant reduction of PGE2 accumulation in the culture medium. In addition, in the same experimental conditions HT incremented the release of TNFα by monocytes. All together, our in vitro data give further support to the hypothesis that olive oil phenols may play a role in the cancer prevention properties of the Mediterranean diet.

Chemopreventive activities of hydroxytyrosol: the major phenol alcohol of extra-virgin olive oil

ROSIGNOLI, Patrizia;FABIANI, Roberto
2014

Abstract

ABSTRACT The beneficial role of extra-virgin olive oil on human health was recently attributed to the presence of minor components, with a particular interest toward the phenolic compounds. The phenolic composition of olive oil is complex and includes hydroxytyrosol (3,4-dihydroxyphenylethanol: HT), tyrosol (hydroxyphenylethanol), the dialdehydic form of elenolic acid linked to hydroxytyrosol or tyrosol (oleocanthal), oleuropein aglycon and lignans. Olive oil phenols, in particular HT, have been deeply investigated in the last past years and it has been showed that this phenol may be involved in the prevention of chronic-degenerative disease, like cardiovascular diseases and cancer, through antioxidant mechanisms. However, the biological effects of olive oil polyphenols are not limited to the antioxidant property. Indeed, several researchers have recently demonstrated that olive oil polyphenols are also able to modulate both gene expression and different pathways involved in the regulation of many physiological and pathological conditions. In this field, we show our recent findings on the in vitro chemopreventive activities of HT. We have demonstrated that HT, at relatively high doses (100µM), is able to inhibit proliferation and to arrest cell cycle progression through the up-regulation of the cyclin dependent protein kinase inhibitors p21 and p27 on HL60 promyelocytic cell line. These effects were associated to the induction of differentiation and apoptosis. The initial stress signal responsible for these effects was the HT-induced extracellular production of H2O2. HT was also able to inhibit the proliferation of human tumour cells derived from colon, prostate and breast, indicating an important role in the prevention of the promotion phase of carcinogenesis. In addition, we have observed by the comet assay that HT, at lower doses (1-10µM), is able to inhibit the oxidative DNA damage in human leukocytes so suggesting a preventive mechanism in the initiation phase of carcinogenesis. These results have allowed us to highlight that HT is able to induce either pro-oxidant or anti-oxidant effects which are depend on exposition doses. Furthermore, we demonstrated that HT (50-100µM) was able to prevent LPS-mediated COX2 induction on human monocytes at both mRNA and protein levels. These effects were associated to a significant reduction of PGE2 accumulation in the culture medium. In addition, in the same experimental conditions HT incremented the release of TNFα by monocytes. All together, our in vitro data give further support to the hypothesis that olive oil phenols may play a role in the cancer prevention properties of the Mediterranean diet.
2014
9781631176623
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1226678
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