Induction of DNA damage by risk factors of colon cancer in human colon cells derived from biopsies

1997 ◽  
Vol 375 (2) ◽  
pp. 105-115 ◽  
Author(s):  
B.L Pool-Zobel ◽  
U Leucht
Keyword(s):  
Risk Factors ◽  
Colon Cancer ◽  
Dna Damage ◽  
Human Colon ◽  
Colon Cells

Putative colon cancer risk factors damage global DNA and TP53 in primary human colon cells isolated from surgical samples

2003 ◽  
Vol 41 (5) ◽  
pp. 655-664 ◽  
Author(s):  
A. Schaeferhenrich ◽  
W. Sendt ◽  
J. Scheele ◽  
A. Kuechler ◽  
T. Liehr ◽  
...  
Keyword(s):  
Risk Factors ◽  
Colon Cancer ◽  
Cancer Risk ◽  
Human Colon ◽  
Colon Cells ◽  
Cancer Risk Factors ◽  
Colon Cancer Risk

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

Abstract 2564: The anticancer molecule TPEN induces DNA damage in human colon cancer cells

2015 ◽  
Author(s):  
Hala Gali-Muhtasib ◽  
Omar Rahal ◽  
Maamoun Fatfat ◽  
Carla Hankache ◽  
Bassam Osman ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

Cocoplum (Chrysobalanus icaco L.) anthocyanins exert anti-inflammatory activity in human colon cancer and non-malignant colon cells

2017 ◽  
Vol 8 (1) ◽  
pp. 307-314 ◽  
Author(s):  
Vinicius P. Venancio ◽  
Paula A. Cipriano ◽  
Hyemee Kim ◽  
Lusânia M. G. Antunes ◽  
Stephen T. Talcott ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Human Colon ◽  
Inflammatory Activity ◽  
Human Colon Cancer ◽  
Colon Cells ◽  
Anti Inflammatory

Cocoplum anthocyanins reduced cell proliferation in cancer cells and decreased inflammation in both non-malignant and cancer cells.

scholarly journals Mismatch Repair Proteins Are Activators of Toxic Responses to Chromium-DNA Damage

2005 ◽  
Vol 25 (9) ◽  
pp. 3596-3607 ◽  
Author(s):  
Elizabeth Peterson-Roth ◽  
Mindy Reynolds ◽  
George Quievryn ◽  
Anatoly Zhitkovich
Keyword(s):  
Dna Damage ◽  
Mismatch Repair ◽  
Dna Adducts ◽  
Human Colon ◽  
Repair System ◽  
Very High Frequency ◽  
Colon Cells ◽  
Lung Cancers ◽  
Toxic Responses

ABSTRACT Chromium(VI) is a toxic and carcinogenic metal that causes the formation of DNA phosphate-based adducts. Cr-DNA adducts are genotoxic in human cells, although they do not block replication in vitro. Here, we report that induction of cytotoxicity in Cr(VI)-treated human colon cells and mouse embryonic fibroblasts requires the presence of all major mismatch repair (MMR) proteins. Cr-DNA adducts lost their ability to block replication of Cr-modified plasmids in human colon cells lacking MLH1 protein. The presence of functional mismatch repair caused induction of p53-independent apoptosis associated with activation of caspases 2 and 7. Processing of Cr-DNA damage by mismatch repair resulted in the extensive formation of γ-H2AX foci in G2 phase, indicating generation of double-stranded breaks as secondary toxic lesions. Induction of γ-H2AX foci was observed at 6 to 12 h postexposure, which was followed by activation of apoptosis in the absence of significant G2 arrest. Our results demonstrate that mismatch repair system triggers toxic responses to Cr-DNA backbone modifications through stress mechanisms that are significantly different from those for other forms of DNA damage. Selection for Cr(VI) resistant, MMR-deficient cells may explain the very high frequency of lung cancers with microsatellite instability among chromate workers.

scholarly journals CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties

2021 ◽  
Vol 9 ◽  
Author(s):  
Shudong Zhu ◽  
Yan Zhu ◽  
Qiuwen Wang ◽  
Yi Zhang ◽  
Xialing Guo
Keyword(s):  
Dna Methylation ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Dna Methyltransferases ◽  
Colon Cancer Cells ◽  
Normal Colon ◽  
Human Colon Cancer ◽  
Colon Cells ◽  
Matrigel Invasion

Src is an important oncogene that plays key roles in multiple signal transduction pathways. Csk-homologous kinase (CHK) is a kinase whose molecular roles are largely uncharacterized. We previously reported expression of CHK in normal human colon cells, and decreased levels of CHK protein in colon cancer cells leads to the activation of Src (Zhu et al., 2008). However, how CHK protein expression is downregulated in colon cancer cells has been unknown. We report herein that CHK mRNA was decreased in colon cancer cells as compared to normal colon cells, and similarly in human tissues of normal colon and colon cancer. Increased levels of DNA methylation at promotor CpG islands of CHK gene were observed in colon cancer cells and human colon cancer tissues as compared to their normal healthy counterparts. Increased levels of DNA methyltransferases (DNMTs) were also observed in colon cancer cells and tissues. DNA methylation and decreased expression of CHK mRNA were inhibited by DNMT inhibitor 5-Aza-CdR. Cell proliferation, colony growth, wound healing, and Matrigel invasion were all decreased in the presence of 5-Aza-CdR. These results suggest that increased levels of DNA methylation, possibly induced by enhanced levels of DNMT, leads to decreased expression of CHK mRNA and CHK protein, promoting increased oncogenic properties in colon cancer cells.

scholarly journals Sam68/KHDRBS1 is critical for colon tumorigenesis by regulating genotoxic stress-induced NF-κB activation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Kai Fu ◽  
Xin Sun ◽  
Eric M Wier ◽  
Andrea Hodgson ◽  
Yue Liu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dna Damage ◽  
Signaling Pathway ◽  
Rna Binding ◽  
Genotoxic Stress ◽  
Human Colon ◽  
Tumor Burden ◽  
Human Colon Cancer ◽  
Nuclear Signaling ◽  
Colon Tumorigenesis

Nuclear factor kappa B (NF-κB)-mediated transcription is an important mediator for cellular responses to DNA damage. Genotoxic agents trigger a 'nuclear-to-cytoplasmic' NF-κB activation signaling pathway; however, the early nuclear signaling cascade linking DNA damage and NF-κB activation is poorly understood. Here we report that Src-associated-substrate-during-mitosis-of-68kDa/KH domain containing, RNA binding, signal transduction associated 1 (Sam68/KHDRBS1) is a key NF-κB regulator in genotoxic stress-initiated signaling pathway. Sam68 deficiency abolishes DNA damage-stimulated polymers of ADP-ribose (PAR) production and the PAR-dependent NF-κB transactivation of anti-apoptotic genes. Sam68 deleted cells are hypersensitive to genotoxicity caused by DNA damaging agents. Upregulated Sam68 coincides with elevated PAR production and NF-κB-mediated anti-apoptotic transcription in human and mouse colon cancer. Knockdown of Sam68 sensitizes human colon cancer cells to genotoxic stress-induced apoptosis and genetic deletion of Sam68 dampens colon tumor burden in mice. Together our data reveal a novel function of Sam68 in the genotoxic stress-initiated nuclear signaling, which is crucial for colon tumorigenesis.

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