Phenolic extract from oleaster (Olea europaea var. Sylvestris) leaves reduces colon cancer growth and induces caspase-dependent apoptosis in colon cancer cells via the mitochondrial apoptotic pathway

Zeriouh, Wafa; Nani, Abdelhafid; Belarbi, Meriem; Dumont, Adélie; Rosny, Charlotte de; Aboura, Ikram; Ghanemi, Fatima Zahra; Murtaza, Babar; Patoli, Danish; Thomas, Charles W.; Apétoh, Lionel; Rébé, Cédric; Delmas, Dominique; Ghiringhelli, François; Rialland, Mickaël; Hichami, Aziz

doi:10.1371/journal.pone.0170823

Cited by 38 publications

(22 citation statements)

References 45 publications

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“…Among these compounds, polyphenols, secondary metabolites of plants that have beneficial effects on human health and reduce the risk of most cancers, have been widely recognized. 22 , 23 Hydroxytyrosol is a natural polyphenol compound and a strong antioxidant. Recent studies have shown that this potent antioxidant has several biological activities, such as oxidative-stress control, cellular efficacy, and induction of apoptosis in several tumor-cell lines.…”

Section: Discussionmentioning

confidence: 99%

<p>Effects of Hydroxytyrosol on Expression of Apoptotic Genes and Activity of Antioxidant Enzymes in LS180 Cells</p>

Hadipour¹,

Marzijerani²,

Baharvand³

2020

CMAR

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Purpose: Colorectal cancer is the third-most commonly occurring cancer in developed countries. Hydroxytyrosol is a potent antioxidant that has several activities, such as oxidative-stress control, inhibition of cell proliferation, and induction of apoptosis. In this study, the effect of hydroxytyrosol on the expression of genes effective in apoptosis-BAX, BCL2, CASP3, P53, PPARG, and NFE2L2-and antioxidant-enzyme activity in LS180 cells of human colorectal cancer was investigated. Methods: The human colorectal cancer cell line LS180 was treated with different concentrations of hydroxytyrosol for 24 hours. Expression of BAX, BCL2, CASP3, NFE2L2, PPARG, and P53 was investigated using real-time PCR. The activity of antioxidant and malondialdehyde enzymes was measured by calorimetric methods. Results: Analysis of gene expression showed that hydroxytyrosol significantly increased the expression of CASP3 and the BAX:BCL2 ratio in treatment groups compared to the control (P<0.05). Also, hydroxytyrosol significantly reduced the expression of the NFE2L2 gene (P<0.05). Calorimetric analysis showed that hydroxytyrosol increased activity of the antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase in treatment groups significantly more than the control group and reduced thiobarbituric acid-reactive substances on an oxidative stress index (P<0.05). Conclusion: Hydroxytyrosol may induce apoptosis in colorectal cancer cells by increasing the expression of CASP3 gene and increasing the BAX:BCL2 ratio. Also, hydroxytyrosol may increase the activity of antioxidant enzymes and reduce the proliferation of LS180 cells by changing the antioxidant-defense system in cancer cells.

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Section: Discussionmentioning

confidence: 99%

<p>Effects of Hydroxytyrosol on Expression of Apoptotic Genes and Activity of Antioxidant Enzymes in LS180 Cells</p>

Hadipour¹,

Marzijerani²,

Baharvand³

2020

CMAR

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“…The early pro survival response inhibits the expression of pro apoptotic C/EBP homologous protein (CHOP). However, prolonged ERS is associated with an increase of ROS levels and IRE-1α/XBP1 mediated activation of both CHOP and Bim and inhibition of Bcl-2, which leads to apoptosis [ 85 , 86 , 87 , 88 , 89 ]. Activation of the PERK pathway leads to phosphorylation of eukaryotic initiation translation factor 2α (eIF2α), which triggers an antioxidant, pro survival response mediated by transcription factor 4 (ATF4).…”

Section: Er Stress Induction and Consequencesmentioning

confidence: 99%

Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors

et al. 2018

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Multidrug resistance (MDR) is a phenotype of cancer cells with reduced sensitivity to a wide range of unrelated drugs. P-glycoprotein (P-gp)—a drug efflux pump (ABCB1 member of the ABC transporter gene family)—is frequently observed to be a molecular cause of MDR. The drug-efflux activity of P-gp is considered as the underlying mechanism of drug resistance against P-gp substrates and results in failure of cancer chemotherapy. Several pathological impulses such as shortages of oxygen and glucose supply, alterations of calcium storage mechanisms and/or processes of protein N-glycosylation in the endoplasmic reticulum (ER) leads to ER stress (ERS), characterized by elevation of unfolded protein cell content and activation of the unfolded protein response (UPR). UPR is responsible for modification of protein folding pathways, removal of misfolded proteins by ER associated protein degradation (ERAD) and inhibition of proteosynthesis. However, sustained ERS may result in UPR-mediated cell death. Neoplastic cells could escape from the death pathway induced by ERS by switching UPR into pro survival mechanisms instead of apoptosis. Here, we aimed to present state of the art information about consequences of P-gp expression on mechanisms associated with ERS development and regulation of the ERAD system, particularly focused on advances in ERS-associated therapy of drug resistant malignancies.

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“…In CRC cell lines, treatment of Phenolic, the extract of the oleaster leaves (PEOL), increases ER stress-mediated apoptosis. The effect of PEOL was inhibited as the usage of ROS scavengers, indicating the involvement of ROS in PEOL induced apoptosis(Zeriouh et al, 2017). Triptolide (PG490) induced apoptosis through ROS in a time-and dose-dependent manner(Tan & Chiu, 2013).Except for showing a cytotoxic effect on CRC cell lines, PG490 also enhanced the cytotoxicity effect of 5-fluorouracil (5-FU) in CRC cell lines in 4-15fold.…”

mentioning

confidence: 99%

Reactive oxygen species and colorectal cancer

Lin¹,

Li²,

Zamyatnin

et al. 2018

Journal Cellular Physiology

124

107

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Colorectal cancer (CRC) has become the fourth leading cause of cancer-related death in the worldwide. It is urgent to find more effective therapeutic strategies for it. Reactive oxygen species (ROS) play multiple roles in normal cellular physiology processes. Thus, a certain level of ROS is essential to keep normal cellular function. However, the accumulation of ROS shows dual roles for cells, which is mainly dependent on the concentration of ROS, the origin of the cancer cell and the activated signaling pathways during tumor progression. In general, moderate level of ROS leads to cell damage, DNA mutation and inflammation, which promotes the initiation and development of cancer. Excessive high level of ROS induces cancer cell death, showing an anti-cancer role. ROS are commonly higher in CRC cells than their normal counterpart cells. Therefore, it is possible that ROS induce cell death in cancer cells while not affecting the normal cells, demonstrating lower side effects. Besides, ROS also play a role in tumor microenvironment and drug resistance. These multiple roles of ROS make them a promising therapeutic target for cancer. To explore potential ROS-target therapies against CRC, it is worth to comprehensively understanding the role of ROS in CRC and therapy. In this review, we mainly discuss the strategies of ROS in CRC therapy, including direct CRC cell target and indirect tumor environment target. In addition, the influences of ROS in drug resistance will also been discussed.

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Phenolic extract from oleaster (Olea europaea var. Sylvestris) leaves reduces colon cancer growth and induces caspase-dependent apoptosis in colon cancer cells via the mitochondrial apoptotic pathway

Cited by 38 publications

References 45 publications

<p>Effects of Hydroxytyrosol on Expression of Apoptotic Genes and Activity of Antioxidant Enzymes in LS180 Cells</p>

<p>Effects of Hydroxytyrosol on Expression of Apoptotic Genes and Activity of Antioxidant Enzymes in LS180 Cells</p>

Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors

Reactive oxygen species and colorectal cancer

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