Methyleugenol and selected oxidative metabolites affect DNA-Damage signalling pathways and induce apoptosis in human colon tumour HT29 cells

2017 ◽  
Vol 108 ◽  
pp. 267-275 ◽  
Author(s):  
Isabel Anna Maria Groh ◽  
Melanie Esselen
Keyword(s):  
Dna Damage ◽  
Human Colon ◽  
Signalling Pathways ◽  
Colon Tumour ◽  
Ht29 Cells ◽  
Oxidative Metabolites ◽  
Dna Damage Signalling

scholarly journals Phosphoproteomic analysis reveals plant DNA damage signalling pathways with a functional role for histone H2 AX phosphorylation in plant growth under genotoxic stress

2019 ◽  
Vol 100 (5) ◽  
pp. 1007-1021 ◽  
Author(s):  
Wanda M. Waterworth ◽  
Michael Wilson ◽  
Dapeng Wang ◽  
Thomas Nuhse ◽  
Stacey Warward ◽  
...  
Keyword(s):  
Dna Damage ◽  
Plant Growth ◽  
Functional Role ◽  
Genotoxic Stress ◽  
Signalling Pathways ◽  
Plant Dna ◽  
Dna Damage Signalling

scholarly journals Topoisomerase poisoning by the flavonoid nevadensin triggers DNA damage and apoptosis in human colon carcinoma HT29 cells

2021 ◽  
Author(s):  
Lena Müller ◽  
Larissa Rhonda Friederike Schütte ◽  
David Bücksteeg ◽  
Julian Alfke ◽  
Thomas Uebel ◽  
...  
Keyword(s):  
Dna Damage ◽  
Colon Carcinoma ◽  
Cellular Response ◽  
Human Colon ◽  
Test System ◽  
Dna Intercalation ◽  
Ht29 Cells ◽  
Human Colon Carcinoma ◽  
The Impact

AbstractNevadensin, an abundant polyphenol of basil, is reported to reduce alkenylbenzene DNA adduct formation. Furthermore, it has a wide spectrum of further pharmacological properties. The presented study focuses the impact of nevadensin on topoisomerases (TOPO) in vitro. Considering the DNA-intercalating properties of flavonoids, first, minor groove binding properties (IC50 = 31.63 µM), as well as DNA intercalation (IC50 = 296.91 µM) of nevadensin, was found. To determine potential in vitro effects on TOPO I and TOPO IIα, the relaxation and decatenation assay was performed in a concentration range of 1–500 µM nevadensin. A partial inhibition was detected for TOPO I at concentrations  ≥ 100 µM, whereas TOPO IIα activity is only inhibited at concentrations  ≥ 250 µM. To clarify the mode of action, the isolating in vivo complex of enzyme assay was carried out using human colon carcinoma HT29 cells. After 1 h of incubation, the amount of TOPO I linked to DNA was significantly increased by nevadensin (500 µM), why nevadensin was characterized as TOPO I poison. However, no effects on TOPO IIα were detected in the cellular test system. As a subsequent cellular response to TOPO I poisoning, a highly significant increase of DNA damage after 2 h and a decrease of cell viability after 48 h at the same concentration range were found. Furthermore, after 24 h of incubation a G2/M arrest was observed at concentrations ≥ 100 µM by flow cytometry. The analysis of cell death revealed that nevadensin induces the intrinsic apoptotic pathway via activation of caspase-9 and caspase-3. The results suggest that cell cycle disruption and apoptotic events play key roles in the cellular response to TOPO I poisoning caused by nevadensin in HT29 cells.

scholarly journals Fermented wheat aleurone induces enzymes involved in detoxification of carcinogens and in antioxidative defence in human colon cells

2010 ◽  
Vol 104 (8) ◽  
pp. 1101-1111 ◽  
Author(s):  
Katrin Stein ◽  
Anke Borowicki ◽  
Daniel Scharlau ◽  
Michael Glei
Keyword(s):  
Dna Damage ◽  
Cancer Prevention ◽  
Mrna Expression ◽  
Human Colon ◽  
Colon Cells ◽  
Antioxidative Defence ◽  
Ht29 Cells ◽  
Expression Of Genes ◽  
Activity Of Enzymes

Dietary fibre is fermented by the human gut flora resulting mainly in the formation of SCFA, for example, acetate, propionate and butyrate. SCFA, in particular butyrate, may be important for secondary cancer prevention by inducing apoptosis and inhibiting cell growth of cancer cells, thereby inhibiting the promotion and/or progression of cancer. Furthermore, SCFA could also act on primary cancer prevention by activation of detoxifying and antioxidative enzymes. We investigated the effects of fermented wheat aleurone on the expression of genes involved in stress response and toxicity, activity of drug-metabolising enzymes and anti-genotoxic potential. Aleurone was digested and fermented in vitro to obtain samples that reflect the content of the colon. HT29 cells and colon epithelial stripes were incubated with the resulting fermentation supernatant fractions (fs) and effects on mRNA expression of CAT, GSTP1 and SULT2B1 and enzyme activity of glutathione S-transferase (GST) and catalase (CAT) were measured. Fermented aleurone was also used to study the protection against H2O2-induced DNA damage in HT29 cells. The fs of aleurone significantly induced the mRNA expression of CAT, GSTP1 and SULT2B1 (HT29) and GSTP1 (epithelial stripes), respectively. The enzyme activities of GST (HT29) and CAT (HT29, epithelial stripes) were also unambiguously increased (1·4- to 3·7-fold) by the fs of aleurone. DNA damage induced by H2O2 was significantly reduced by the fs of aleurone after 48 h, whereupon no difference was observed compared with the faeces control. In conclusion, fermented aleurone is able to act on primary prevention by inducing mRNA expression and the activity of enzymes involved in detoxification of carcinogens and antioxidative defence.

scholarly journals Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helena de Castro e Gloria ◽  
Laura Jesuíno Nogueira ◽  
Patrícia Bencke Grudzinski ◽  
Paola Victória da Costa Ghignatti ◽  
Temenouga Nikolova Guecheva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Mismatch Repair ◽  
Cell Cycle Progression ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Human Colon ◽  
Human Colon Cancer

Abstract Background The advances in colorectal cancer (CRC) treatment include the identification of deficiencies in Mismatch Repair (MMR) pathway to predict the benefit of adjuvant 5-fluorouracil (5-FU) and oxaliplatin for stage II CRC and immunotherapy. Defective MMR contributes to chemoresistance in CRC. A growing body of evidence supports the role of Poly-(ADP-ribose) polymerase (PARP) inhibitors, such as Olaparib, in the treatment of different subsets of cancer beyond the tumors with homologous recombination deficiencies. In this work we evaluated the effect of Olaparib on 5-FU cytotoxicity in MMR-deficient and proficient CRC cells and the mechanisms involved. Methods Human colon cancer cell lines, proficient (HT29) and deficient (HCT116) in MMR, were treated with 5-FU and Olaparib. Cytotoxicity was assessed by MTT and clonogenic assays, apoptosis induction and cell cycle progression by flow cytometry, DNA damage by comet assay. Adhesion and transwell migration assays were also performed. Results Our results showed enhancement of the 5-FU citotoxicity by Olaparib in MMR-deficient HCT116 colon cancer cells. Moreover, the combined treatment with Olaparib and 5-FU induced G2/M arrest, apoptosis and polyploidy in these cells. In MMR proficient HT29 cells, the Olaparib alone reduced clonogenic survival, induced DNA damage accumulation and decreased the adhesion and migration capacities. Conclusion Our results suggest benefits of Olaparib inclusion in CRC treatment, as combination with 5-FU for MMR deficient CRC and as monotherapy for MMR proficient CRC. Thus, combined therapy with Olaparib could be a strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.

O XVII B.2 Determination of endogenous DNA damage, oxidated DNA bases and oxidative stress in primary human colon cells and modulation by plant ingredients

1997 ◽  
Vol 379 (1) ◽  
pp. S171
Author(s):  
Beatrice L. Pool-Zobel ◽  
Salomon L. Abrahamse ◽  
Daniela Oberreuther ◽  
Sylvia Treptow-van Lishaut ◽  
Gerhard Rechkemmer
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Human Colon ◽  
Dna Bases ◽  
Colon Cells ◽  
And Oxidative Stress

scholarly journals Cleavage and Inactivation of ATM during Apoptosis

1999 ◽  
Vol 19 (9) ◽  
pp. 6076-6084 ◽  
Author(s):  
Graeme C. M. Smith ◽  
Fabrizio d’adda di Fagagna ◽  
Nicholas D. Lakin ◽  
Stephen P. Jackson
Keyword(s):  
Dna Damage ◽  
Dna Binding ◽  
Caspase 3 ◽  
Cysteine Proteases ◽  
Dominant Negative ◽  
Protein Kinase Activity ◽  
Dna Damage Signalling ◽  
In Cells

ABSTRACT The activation of the cysteine proteases with aspartate specificity, termed caspases, is of fundamental importance for the execution of programmed cell death. These proteases are highly specific in their action and activate or inhibit a variety of key protein molecules in the cell. Here, we study the effect of apoptosis on the integrity of two proteins that have critical roles in DNA damage signalling, cell cycle checkpoint controls, and genome maintenance—the product of the gene defective in ataxia telangiectasia, ATM, and the related protein ATR. We find that ATM but not ATR is specifically cleaved in cells induced to undergo apoptosis by a variety of stimuli. We establish that ATM cleavage in vivo is dependent on caspases, reveal that ATM is an efficient substrate for caspase 3 but not caspase 6 in vitro, and show that the in vitro caspase 3 cleavage pattern mirrors that in cells undergoing apoptosis. Strikingly, apoptotic cleavage of ATM in vivo abrogates its protein kinase activity against p53 but has no apparent effect on the DNA binding properties of ATM. These data suggest that the cleavage of ATM during apoptosis generates a kinase-inactive protein that acts, through its DNA binding ability, in a trans-dominant-negative fashion to prevent DNA repair and DNA damage signalling.

Induction of G2/M Arrest and Apoptosis by the Methanol Extract of Typha orientalis in Human Colon Adenocarcinoma HT29 Cells

2013 ◽  
Vol 41 (4) ◽  
pp. 425-432 ◽  
Author(s):  
Soojung Jin ◽  
Seung-Geun Yun ◽  
You Na Oh ◽  
Ji-Young Lee ◽  
Hyun-jin Park ◽  
...  
Keyword(s):  
Methanol Extract ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Ht29 Cells ◽  
Typha Orientalis ◽  
Human Colon Adenocarcinoma

scholarly journals ATM kinase activity modulates cFLIP protein levels: potential interplay between DNA damage signalling and TRAIL-induced apoptosis

2010 ◽  
Vol 31 (11) ◽  
pp. 1956-1963 ◽  
Author(s):  
Venturina Stagni ◽  
Michele Mingardi ◽  
Simonetta Santini ◽  
Danilo Giaccari ◽  
Daniela Barilà
Keyword(s):  
Dna Damage ◽  
Kinase Activity ◽  
Atm Kinase ◽  
Protein Levels ◽  
Induced Apoptosis ◽  
Dna Damage Signalling
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