Anti-proliferative and pro-apoptotic activities of hydroxytyrosol on different tumour cells: the role of extracellular production of hydrogen peroxide

Fabiani, Roberto; Sepporta, Maria Vittoria; Rosignoli, Patrizia; Bartolomeo, Angelo De; Crescimanno, Maria; Morozzi, Guido

doi:10.1007/s00394-011-0230-3

Cited by 62 publications

(58 citation statements)

References 44 publications

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“…Indeed, the anti-proliferative activity of 3,4-DHPEA has been widely investigated in several tumour cell types. 22,23 Therefore the variability of anti-proliferative results may depend upon both the capability of cells to eliminate H 2 O 2 by specific enzymes such as catalase and glutathione peroxidase, and the effectiveness by which 3,4-DHPEA releases H 2 O 2 in different cell culture media. 14,[17][18][19][20][21] We have recently investigated the anti-proliferative action of 3,4-DHPEA in different tumour cell lines and we found that the medium used for cell culture was responsible for the different sensibility observed by various authors on different cell lines.…”

Section: Introductionmentioning

confidence: 99%

In vitro chemo-preventive activities of hydroxytyrosol: the main phenolic compound present in extra-virgin olive oil

et al. 2016

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The co-incubation in the culture medium with hydroxytyrosol [3,4-dihydroxyphenyl ethanol (3,4-DHPEA)], the main phenolic compound present in extra-virgin olive oil, and H2O2 reduces the oxidative DNA damage in peripheral blood mononuclear cells (PBMC). In this study we investigate, by the comet assay, the ability of 3,4-DHPEA to inhibit the H2O2 induced DNA damage when pre-incubated with PBMC and then removed before the exposure of cells to H2O2. Low doses of 3,4-DHPEA (10-100 μM) pre-incubated for 30 min with PBMC reduced the DNA damage induced by the treatment with H2O2 200 μM for 5 min at 4 °C. Prolonging the exposure time up to 6 h completely prevented the DNA damage. Furthermore we extensively analysed, by the MTT assay, the anti-proliferative activities of 3,4-DHPEA on breast (MDA and MCF-7), prostate (LNCap and PC3) and colon (SW480 and HCT116) cancer cell lines and correlated these effects with the H2O2 accumulation. The concentration of H2O2 in the culture medium was measured by the ferrous ion oxidation-xylenol orange method. The proliferation of all the cell lines was inhibited but at different levels: the prostate cancer cells were more resistant to the growth inhibition with respect to breast and colon cancer cells. The ability of the different cell lines to remove H2O2 from the culture medium was inversely correlated with their sensitivity to the anti-proliferative effect of 3,4-DHPEA. Therefore, 3,4-DHPEA may act as a chemopreventive agent acting on both initiation and promotion/progression phases of carcinogenesis.

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Section: Introductionmentioning

confidence: 99%

In vitro chemo-preventive activities of hydroxytyrosol: the main phenolic compound present in extra-virgin olive oil

et al. 2016

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“…In fact, depending on HTyr concentrations and cell culture media, HTyr can generate H 2 O 2 in vitro [50,54]. It was indicated that the main initiation step in the H 2 O 2 -producing activity is the auto-oxidation of HTyr by O 2 , leading to the formation of semiquinone O 2 -and 2H + [54].…”

Section: Htyr-mediated Antioxidant Activity and Cancermentioning

confidence: 99%

“…Another unclear point is represented by the reachable plasma concentrations of HTyr following HTyr administration. The large difference in plasma HTyr concentrations reported in the literature is mostly correlated to the difference in the bioavailability of HTyr [54][55][56]. The administration of HTyr as olive oil ingestion, that is HTyr associated with lipids and other polyphenols, lead to the absorption of approximately 44% of the total HTyr amount [55].…”

Section: Hydroxytyrosol and Cancermentioning

confidence: 99%

“…Then, the same authors [101] reported that HTyr (100 GM) decreases the expression of Cdk6 and increased that of Cdk inhibitors p21 WAF/Cip1 and p27 Kip1 in the same cell type. They also proposed that HTyr-mediated apoptosis was due to both extracellular H 2 O 2 production induced by the abovementioned HTyr-mediated pro-oxidant activity and the Michael addition reaction between HTyrQ and thiol groups in proteins, promoting endoplasmic reticulum (ER)-dependent stress with the consequent activation of pro-apoptotic signals [54,102]. However, in contrast to Della Ragione et al [95], no effect on apoptosis was observed on freshly isolated human lymphocytes and polymorphonuclear cells by Fabiani et al [99].…”

Section: Htyr-mediated Antiproliferative Activity and Cancermentioning

confidence: 99%

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Naturally Occurring Hydroxytyrosol: Synthesis and Anticancer Potential

Bernini¹,

Merendino²,

Romani³

et al. 2013

CMC

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Several epidemiological and animal studies have suggested that polyphenols, a group of secondary plant metabolites occurring mainly in the plant kingdom, may have a protective effect against some chronic degenerative diseases such as cancer. Polyphenols are part of the human diet, being present in vegetal food and beverages. Among them, an olive biophenol named hydroxytyrosol [2-(3,4-dihydroxyphenyl)ethanol, HTyr] has recently received particular attention because of its antioxidant, antiproliferative, pro-apoptotic, and anti-inflammatory activities, which have the potential to specifically counteract all cancer hallmarks, thus representing the expectant biological activities underlying the anti-tumor properties of this polyphenol. After a description of the synthetic procedures to prepare pure HTyr, this review takes into consideration the chemopreventive and chemotherapeutic potential of HTyr as the result of its antioxidant, antiproliferative and anti-inflammatory activities. In particular, the review is focused on the current knowledge of the main cellular and molecular mechanisms used by HTyr to affect carcinogenesis, highlighting the specific oncogenic and inflammatory signaling pathways potentially targeted by HTyr.

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“…Two separate cell lines were used for each of the breast, prostate and colon cancer types, and different IC50 values were found. The fact that the abilities of different cancer cell lines to remove H2O2 accumulating in the culture medium are different from one another affects the susceptibility of the cells to the anti-proliferative effect of HT 18 . In our study, two different ovarian cancer cell lines were used.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic and Apoptotic Effects of Hydroxytyrosol on Ovarian Cancer Cell Lines: Relationship of Cytotoxic Effect with ERK 1/2 Pathway

Oktay¹,

Tuğrul²

2016

Cumhuriyet Med J

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SUMMARYObjective: It has been shown that hydroxytryrosol (HT) has antitumoral, anti-proliferative and apoptotic effects on various cancer cell line types. In this study, we investigated cytotoxic and apoptotic effects of HTon human ovarian cancer cell lines OVCAR-3 and MDAH-2774 and relationship of its cytotoxic effects with phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways. Method: XTT cell proliferation kit, Cell Death Detection Elisa Plus Kit and Human Apoptosis Array test were used to determine the cytotoxic and apoptotic effects of HT in OVCAR-3 and MDAH-2774 cell lines at 24, 48, 72 and 96 hours (h). Effect of HT on PI3K/Akt and ERK 1/2 signaling pathways were investigated by using specific inhibitors of these pathways. Results: IC50 values of HT were found to be 102.3 μM in MDAH-2774 cells at 72 h and 51.5 μM in OVCAR-3 cells at 96 h. Highest apoptotic effect was seen at 100 μM concentration in OVCAR-3 cells at 96 h and at 50 μM at 72 h in MDAH-2774. HT increased the levels of pro-apoptotic molecules including Bad, Bax, active caspase-3, Htra2/Omi and of proapoptotic death receptors TRAIL R1/DR4, TRAIL R2/DR5, FAS/TNFRSF6 and decreased Survivin levels in MDAH-2774 cells. In OVCAR-3 cells, HT decreased Bcl-2, pro-caspase 3 and CIAP-1, CIAP-2, XIAP, Livin, Survivin levels and increased cytochrome-c level. The cell vitality was increased in both of the cell lines as the result of the treatment with HT and FR180204. Conclusions: These results show that HT has potential cytotoxic and apoptotic effect on OVCAR-3 and MDAH-2774 cells. In both cell lines, the cytotoxic effect of HT could be ocur inhibiting through ERK 1/2 signaling pathway.

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Anti-proliferative and pro-apoptotic activities of hydroxytyrosol on different tumour cells: the role of extracellular production of hydrogen peroxide

Abstract: The pro-oxidant activity of 3,4-DHPEA deeply influences its 'in vitro' chemopreventive activities. The main initiation step in the H₂O₂-producing activity is the auto-oxidation of 3,4-DHPEA by O₂ with the formation of the semiquinone, superoxide ions (O₂(-)) and 2H(+).

Cited by 62 publications

References 44 publications

In vitro chemo-preventive activities of hydroxytyrosol: the main phenolic compound present in extra-virgin olive oil

In vitro chemo-preventive activities of hydroxytyrosol: the main phenolic compound present in extra-virgin olive oil

Naturally Occurring Hydroxytyrosol: Synthesis and Anticancer Potential

Cytotoxic and Apoptotic Effects of Hydroxytyrosol on Ovarian Cancer Cell Lines: Relationship of Cytotoxic Effect with ERK 1/2 Pathway

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