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Hydroxytyrosol Induces Apoptosis In Human Colon Cancer Cells Through ROS Generation.

Lijuan Sun, Cheng Luo, J. Liu
Published 2014 · Biology, Medicine

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Cancer cells are usually under higher levels of oxidative stress compared to normal cells. We hypothesized that the introduction of additional reactive oxygen species (ROS) or the suppression of antioxidant activity may selectively enhance cancer cell killing by generating oxidative agents through stress overload or stress sensitization. The aim of this work was to test whether hydroxytyrosol (HT), one of the major polyphenolic constituents of extra virgin olive oil, could exert anti-cancer effects on human colon adenocarcinoma cells via its ability to induce apoptosis through ROS generation. HT exhibits preferential anti-proliferative effects on human colon cancer cells (DLD1 cells) but not on normal colon epithelial 1807 cells. HT causes oxidative stress, activates the phosphoinositide 3-kinase/Akt pathway, phosphorylates FOXO3a and then downregulates FOXO3a's target genes. Combined with SOD or catalase treatment, there are different responses in HT-treated DLD1 cells. The results support the hypothesis that the two main species of ROS, superoxide and H2O2, play different roles in cancer cell survival. The present work shows that HT induces apoptotic cell death and mitochondrial dysfunction by generating ROS in colon cancer cells. This research presents important evidence on the in vitro chemopreventive effect of HT and shows that the disruption of the intrinsic redox status promotes cancer cell death.
This paper references
10.1667/3099
Adaptation of the Dichlorofluorescein Assay for Detection of Radiation-Induced Oxidative Stress in Cultured Cells
X. Wan (2003)
10.1016/J.CCR.2005.08.008
The Akt-mTOR tango and its relevance to cancer.
N. Hay (2005)
10.1016/j.abb.2010.06.012
Instability of, and generation of hydrogen peroxide by, phenolic compounds in cell culture media.
L. Long (2010)
10.1111/j.1471-4159.2007.04954.x
Hydroxytyrosol protects retinal pigment epithelial cells from acrolein‐induced oxidative stress and mitochondrial dysfunction
Zhongbo Liu (2007)
10.1016/J.DEVCEL.2007.03.020
The two TORCs and Akt.
Prashanth T. Bhaskar (2007)
10.1016/S1357-2725(99)00088-6
Role of reactive oxygen species in apoptosis: implications for cancer therapy.
J. M. Matés (2000)
10.1006/BBRC.2000.3875
Hydroxytyrosol, a natural molecule occurring in olive oil, induces cytochrome c-dependent apoptosis.
F. D. Ragione (2000)
10.1096/fj.00-0561fje
Functional mitochondria are required for amyloid β‐mediated neurotoxicity
S. Cardoso (2001)
10.1016/S0014-5793(99)01258-2
Superoxide anion inhibits drug‐induced tumor cell death
S. Pervaiz (1999)
10.1016/J.BIOCEL.2007.04.007
Superoxide anion: oncogenic reactive oxygen species?
S. Pervaiz (2007)
10.1073/PNAS.0408894102
mtDNA mutations increase tumorigenicity in prostate cancer.
J. Petros (2005)
10.1089/ARS.2005.7.456
Production of intracellular superoxide mediates dithiothreitol-dependent inhibition of apoptotic cell death.
M. Clément (2005)
10.1016/S0304-4165(01)00230-6
Kinetic analysis and mechanistic aspects of autoxidation of catechins.
M. Mochizuki (2002)
10.1158/0008-5472.CAN-07-5259
Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype.
B. Kumar (2008)
10.1089/ars.2010.3851
Bcl-2: a prime regulator of mitochondrial redox metabolism in cancer cells.
I. Low (2011)
10.1093/JN/138.1.42
Inhibition of cell cycle progression by hydroxytyrosol is associated with upregulation of cyclin-dependent protein kinase inhibitors p21(WAF1/Cip1) and p27(Kip1) and with induction of differentiation in HL60 cells.
R. Fabiani (2008)
10.1038/sj.bjp.0701722
The possible mechanisms of the antiproliferative effect of fullerenol, polyhydroxylated C60, on vascular smooth muscle cells
L. Lu (1998)
10.1111/J.1753-4887.2005.TB00374.X
Components of olive oil and chemoprevention of colorectal cancer.
Y. Z. H. Hashim (2005)
10.1016/S0014-5793(98)01410-0
Apoptosis induced by hydrogen peroxide is mediated by decreased superoxide anion concentration and reduction of intracellular milieu
M. Clément (1998)
10.1002/1097-0142(20000701)89:1<123::AID-CNCR17>3.0.CO;2-9
Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer
D. Bostwick (2000)
10.1007/s10616-009-9191-2
Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells
J. Han (2009)
10.1016/j.ccr.2008.11.003
Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis.
V. Nogueira (2008)
10.1196/annals.1299.067
Pro‐oxidant Activity of Low Doses of Resveratrol Inhibits Hydrogen Peroxide—Induced Apoptosis
K. A. Ahmad (2003)
10.2174/15680096113139990035
Hydroxytyrosol promotes superoxide production and defects in autophagy leading to anti-proliferation and apoptosis on human prostate cancer cells.
C. Luo (2013)
10.1158/0008-5472.CAN-09-4572
A NADPH oxidase-dependent redox signaling pathway mediates the selective radiosensitization effect of parthenolide in prostate cancer cells.
Y. Sun (2010)
10.1158/0008-5472.CAN-03-2414
Resveratrol Inhibits Drug-Induced Apoptosis in Human Leukemia Cells by Creating an Intracellular Milieu Nonpermissive for Death Execution
K. A. Ahmad (2004)
10.1002/ijc.21083
Potential anti‐cancer effects of virgin olive oil phenolson colorectal carcinogenesis models in vitro
C. Gill (2005)
10.1097/00008469-200208000-00006
Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis
R. Fabiani (2002)
10.1016/0022-1759(83)90303-4
Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.
T. Mosmann (1983)
10.1016/j.jnutbio.2009.03.012
Hydroxytyrosol promotes mitochondrial biogenesis and mitochondrial function in 3T3-L1 adipocytes.
Jiejie Hao (2010)
10.1016/j.jnutbio.2009.09.006
Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal pigment epithelial cells.
L. Zhu (2010)
10.1023/A:1015913229650
Redox signaling
H. Forman (2004)
10.1016/j.jnutbio.2011.05.006
Stimulation of GSH synthesis to prevent oxidative stress-induced apoptosis by hydroxytyrosol in human retinal pigment epithelial cells: activation of Nrf2 and JNK-p62/SQSTM1 pathways.
Xuan Zou (2012)
10.1002/mnfr.200800269
Hydroxytyrosol inhibits the proliferation of human colon adenocarcinoma cells through inhibition of ERK1/2 and cyclin D1.
Giulia Corona (2009)
10.1002/mnfr.201000220
Hydroxytyrosol inhibits growth and cell proliferation and promotes high expression of sfrp4 in rat mammary tumours.
S. Granados-Principal (2011)
10.1007/s00394-011-0230-3
Anti-proliferative and pro-apoptotic activities of hydroxytyrosol on different tumour cells: the role of extracellular production of hydrogen peroxide
R. Fabiani (2011)
10.1093/JN/136.3.614
Virgin olive oil phenols inhibit proliferation of human promyelocytic leukemia cells (HL60) by inducing apoptosis and differentiation.
R. Fabiani (2006)



This paper is referenced by
10.1016/j.arcmed.2016.06.006
Effect of Hydroxytyrosol on Human Mesenchymal Stromal/Stem Cell Differentiation into Adipocytes and Osteoblasts.
J. Anter (2016)
10.3390/ijms21218074
The Hydroxytyrosol Induces the Death for Apoptosis of Human Melanoma Cells
F. Costantini (2020)
10.12677/BIPHY.2015.31004
Structures, Antioxidation Mechanism, and Antioxidation Test of the Common Natural Antioxidants in Plants
何 慧娟 (2015)
10.1186/s12970-018-0221-3
Effects of hydroxytyrosol dose on the redox status of exercised rats: the role of hydroxytyrosol in exercise performance
S. Al Fazazi (2018)
10.1186/s41702-018-0031-x
Anti-inflammatory and anti-aging effects of hydroxytyrosol on human dermal fibroblasts (HDFs)
Seeun Jeon (2018)
10.3892/or.2016.5150
Extra-virgin olive oil phenols block cell cycle progression and modulate chemotherapeutic toxicity in bladder cancer cells
Andrea Coccia (2016)
10.1016/j.nut.2017.06.008
Mediterranean diet and colorectal cancer: A systematic review.
A. Farinetti (2017)
10.5539/jfr.v8n1p60
Selected Powerful Natural Antioxidants: Structure, Food Sources, Antioxidant Activities and Important Health Benefits
B. Nemzer (2019)
10.1016/j.foodres.2017.11.053
Hydroxytyrosol: Bioavailability, toxicity, and clinical applications.
María Robles-Almazán (2018)
10.1016/j.bbrc.2017.06.084
Aloe-emodin (AE) nanoparticles suppresses proliferation and induces apoptosis in human lung squamous carcinoma via ROS generation in vitro and in vivo.
Yuan-yuan Wu (2017)
10.1039/c5fo00097a
Dual protection of hydroxytyrosol, an olive oil polyphenol, against oxidative damage in PC12 cells.
S. Peng (2015)
10.1080/01635581.2017.1339818
Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells
H. Zubair (2017)
10.1111/1750-3841.14198
Antitumor Perspectives of Oleuropein and Its Metabolite Hydroxytyrosol: Recent Updates.
M. Imran (2018)
10.1007/s00253-014-6310-6
The antioxidant hydroxytyrosol: biotechnological production challenges and opportunities
Y. Achmon (2014)
10.3390/molecules23020404
Thermal Decomposition Behavior of Hydroxytyrosol (HT) in Nitrogen Atmosphere Based on TG-FTIR Methods
Jun-Ling Tu (2018)
10.1039/c8fo00165k
The inhibitory effect of Manuka honey on human colon cancer HCT-116 and LoVo cell growth. Part 2: Induction of oxidative stress, alteration of mitochondrial respiration and glycolysis, and suppression of metastatic ability.
S. Afrin (2018)
10.1039/c5fo00928f
Hydroxytyrosol decreases the oxidative and nitrosative stress levels and promotes angiogenesis through HIF-1 independent mechanisms in renal hypoxic cells.
E. Martı́nez-Lara (2016)
10.1038/s41598-020-63417-6
Crosstalk between hydroxytyrosol, a major olive oil phenol, and HIF-1 in MCF-7 breast cancer cells
J. Calahorra (2020)
10.3892/OL.2016.4708
Dual role of macrophages in the response of C26 colon carcinoma cells to 5-fluorouracil administration.
L. Patras (2016)
10.1016/j.jbiotec.2019.12.016
Hydroxytyrosol: a natural compound with promising pharmacological activities.
M. Bertelli (2019)
10.23751/PN.V20I1-S.5623
New findings on the pharmacodynamic actions of olive oil: our contribution to better evidence about its remedial properties
N. Duborija-Kovačević (2018)
Structures, Antioxidation Mechanism, and Antioxidation Test of the Common Natural Antioxidants in Plants
H. He (2015)
10.3390/ijms19082305
Phenolic Compounds Isolated from Olive Oil as Nutraceutical Tools for the Prevention and Management of Cancer and Cardiovascular Diseases
P. Reboredo-Rodríguez (2018)
10.1016/j.phrs.2019.01.045
Secoiridoids of olive and derivatives as potential coadjuvant drugs in cancer: A critical analysis of experimental studies
M. Celano (2019)
10.1016/j.semcancer.2017.08.005
In vitro polyphenol effects on apoptosis: An update of literature data.
V. Curti (2017)
10.3390/ijerph17124404
Hydroxytyrosol Promotes Proliferation of Human Schwann Cells: An In Vitro Study
Khidhir Kamil (2020)
10.1016/j.plaphy.2017.05.006
Isolation and characterization of Cepa2, a natural alliospiroside A, from shallot (Allium cepa L. Aggregatum group) with anticancer activity.
M. Abdelrahman (2017)
10.15406/JABB.2018.05.00146
Natural antioxidants–properties and possible applications
E. Zymanczyk-Duda (2018)
10.1155/2017/8416763
Oxidative Stress: Harms and Benefits for Human Health
G. Pizzino (2017)
10.1016/j.foodchem.2016.10.111
Hydroxytyrosol targets extracellular matrix remodeling by endothelial cells and inhibits both ex vivo and in vivo angiogenesis.
Javier A. García-Vilas (2017)
10.3389/fnut.2020.00120
An Industrial and Sustainable Platform for the Production of Bioactive Micronized Powders and Extracts Enriched in Polyphenols From Olea europaea L. and Vitis vinifera L. Wastes
Annalisa Romani (2020)
10.1177/1535370216654226
Original Research: Hydroxytyrosol, an ingredient of olive oil, reduces triglyceride accumulation and promotes lipolysis in human primary visceral adipocytes during differentiation
B. Stefanon (2016)
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