Hydroxytyrosol, a natural molecule occurring in olive oil, induces cytochrome c-dependent apoptosis

2-(3,4-Dihydroxyphenyl) ethanol (DPE), a naturally occurring phenolic antio xidant molecule found in olive oil, has been reported to exert several biol ogical and pharmacological activities. We studied the effect of this compou nd on the proliferation and survival of HL60 cell line. Concentrations from 50 to 100 muM DPE, comparable to its olive oil content, caused a complete arrest of HL60 cell proliferation and the induction of apoptosis. This was demonstrated by flow cytometric analyses, poly(ADP-ribose) polymerase cleav age, and caspase 3 activation. The apoptotic effect requires the presence o f two ortho-hydroxyl groups on the phenyl ring, since tyrosol, 2-(4-hydroxy phenyl)ethanol, did not induce either cell growth arrest or apoptosis. DPE- dependent apoptosis is associated with an early release of cytochrome c fro m mitochondria which precedes caspase 8 activation, thus ruling out the eng agement of cell death receptors in the apoptotic process. 2- (3,4-Dihydroxy phenyl) ethanol induced cell death in quiescent and differentiated HL60 cel ls, as well as in resting and activated peripheral blood lymphocytes, while did not cause cell death in two colorectal cell lines (HT-29 and CaCo2). T hese results suggest that DPE down-regulates the immunological response, th us explaining the well-known antinflammatory and chemopreventive effects of olive oil at the intestinal level. (C) 2000 Academic Press.