Hydroxytyrosol, a Natural Molecule Occurring in Olive Oil, Induces Cytochrome c-Dependent Apoptosis

Ragione, Fulvio Della; Cucciolla, Valeria; Borriello, Adriana; Pietra, Valentina Della; Pontoni, Gabriele; Means, Anthony; Manna, Caterina; Galletti, Patrizia; Zappia, Vincenzo

doi:10.1006/bbrc.2000.3875

Cited by 85 publications

(55 citation statements)

References 24 publications

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“…Indeed, it possesses a clear scavenging activity toward different free radicals [3] and it is able to prevent several forms of damage caused by reactive oxygen species (ROS) such as hydrogen peroxide-induced DNA strand breaks in Jurkat [4] and prostate [5] cancer cells, and DNA-base modification induced by peroxynitrite [6]. However, the chemopreventive capacity of 3,4-DHPEA could also be related to its ability to inhibit proliferation and to induce apoptosis and differentiation in different cancer cell lines as demonstrated by previous studies conducted in our laboratory [7] and by other investigators [8].…”

Section: Introductionmentioning

confidence: 89%

Production of hydrogen peroxide is responsible for the induction of apoptosis by hydroxytyrosol on HL60 cells

Fabiani

Fuccelli

Pieravanti

et al. 2009

Molecular Nutrition Food Res

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Hydroxytyrosol [3,4-dihydroxyphenylethanol (3,4-DHPEA)], a phenolic compound found exclusively in olive oil, exerts growth-suppressive and pro-apoptotic effects on different cancer cells. Although some molecular mechanisms involved in the pro-apoptotic activity of 3,4-DHPEA have been proposed, the initial stress signals responsible of this phenomenon are not known. Our aim was to assess the involvement of reactive oxygen species as mediators of apoptosis induced by 3,4-DHPEA on HL60 cells. Apoptosis was determined by analyzing the nuclear fragmentation by both fluorescence microscopy and flow cytometry. The externalization of phosphatidylserine was evidenced using an Annexin V-FITC kit. The concentration of H(2)O(2) in the culture medium was measured by the ferrous ion oxidation-xylenol orange method. The pro-apoptotic effect of 3,4-DHPEA (100 muM) was prevented by N-acetyl-cysteine, ascorbate, and alpha-tocopherol. Catalase suppressed the 3,4-DHPEA-induced apoptosis, while the Fe(II)-chelating reagent o-phenantroline showed no effect, suggesting the involvement of H(2)O(2 )but not of OH(*). Indeed, 3,4-DHPEA caused accumulation of H(2)O(2) in the culture medium. Tyrosol (p-hydroxyphenylethanol) and caffeic acid, compounds structurally similar to 3,4-DHPEA but not able to generate H(2)O(2), did not induce an appreciable apoptotic effect. This is the first study demonstrating that apoptosis induction by 3,4-DHPEA is mediated by the extracellular production of H(2)O(2).

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Section: Introductionmentioning

confidence: 89%

Production of hydrogen peroxide is responsible for the induction of apoptosis by hydroxytyrosol on HL60 cells

Fabiani

Fuccelli

Pieravanti

et al. 2009

Molecular Nutrition Food Res

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“…The aglyconic form of oleuropein and ligstroside, 3,4-DHPEA-EA and p-HPEA-EA respectively, were reported for the first time by Montedoro et al, who also assigned their chemical structures, later confirmed by other (Montedoro et al, 1992;Angerosa et al, 1996;Owen et al, 2000). 3,4-DHPEA-EA and p-HPEA-EA, associated to the intense sensory of bitterness and pungency respectively attribute in VOO (Gutierrez-Rosales et al, 2003), is endowed with numerous beneficial effects on human health (Servili et al, 2004;Bendini et al, 2007;Esti et al, 1998;Della Ragione et al, 2000;Paiva-Martins et al, 2001;Fabiani et al, 2002;Carasco-Pancorbo et al, 2005;Artajo et al, 2006;Fabiani et al, 2006;Fabiani et al, 2008;Paiva-Martins et al, 2009). In particular, the anti-inflammatory properties of olive oil phenolic compounds seem to overlap with those attributed to non-steroidal anti-inflammatory drugs (Procopio A, et al, 2009).…”

Section: Introductionmentioning

confidence: 93%

Oleuropein an Olive Oil Compound in Acute and Chronic Inflammation Models: Facts and Perspectives

Britti¹,

Impellizzeri²,

Procopio³

et al. 2012

Olive Germplasm - The Olive Cultivation, Table Olive and Olive Oil Industry in Italy

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“…Much research has concentrated on different plant extracts' abilities to induce apoptosis of cancer cells. [3][4][5] Overwhelming evidence indicates the involvement of caspases in apoptosis. Caspases make up of a family of cysteine proteases that cleave substrates after aspartic residue.…”

mentioning

confidence: 99%

Apoptosis Induced by Dioscin in Hela Cells.

Cai

Liu

Zhao

et al. 2002

Biological & Pharmaceutical Bulletin

102

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Dioscin, a saponin extracted from the root of Polygonatum Zanlanscianense Pamp, markedly inhibited proliferation of Hela cells. The results indicated that Hela cells underwent apoptosis in dose-and time-dependent manners when treated with Dioscin. Caspase-3, -8 and -9 activities were also detected. The low enzymatic activity of caspase-8 and high activity of caspase-9 showed that the mitochondrial pathway was activated in apoptosis. The reduced expression of the survival protein Bcl-2 also confirmed this result. These studies may be significant in finding a new drug to treat human cervical cancer.

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Hydroxytyrosol, a Natural Molecule Occurring in Olive Oil, Induces Cytochrome c-Dependent Apoptosis

Cited by 85 publications

References 24 publications

Production of hydrogen peroxide is responsible for the induction of apoptosis by hydroxytyrosol on HL60 cells

Production of hydrogen peroxide is responsible for the induction of apoptosis by hydroxytyrosol on HL60 cells

Oleuropein an Olive Oil Compound in Acute and Chronic Inflammation Models: Facts and Perspectives

Apoptosis Induced by Dioscin in Hela Cells.

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