scholarly journals CD95 ligand induces senescence in mismatch repair-deficient human colon cancer via chronic caspase-mediated induction of DNA damage

2017 ◽  
Vol 8 (3) ◽  
pp. e2669-e2669 ◽  
Author(s):  
Danielle A Raats ◽  
Nicola Frenkel ◽  
Susanne J van Schelven ◽  
Inne HMBorel Rinkes ◽  
Jamila Laoukili ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dna Damage ◽  
Mismatch Repair ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Cd95 Ligand

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.

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

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.

scholarly journals Key role of ATF3 in p53-dependent DR5 induction upon DNA damage of human colon cancer cells

Oncogene ◽  
2011 ◽  
Vol 31 (17) ◽  
pp. 2210-2221 ◽  
Author(s):  
K Taketani ◽  
J Kawauchi ◽  
M Tanaka-Okamoto ◽  
H Ishizaki ◽  
Y Tanaka ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

scholarly journals Chk1 and DNA-PK mediate TPEN-induced DNA damage in a ROS dependent manner in human colon cancer cells

2016 ◽  
Vol 17 (11) ◽  
pp. 1139-1148 ◽  
Author(s):  
Omar Nasser Rahal ◽  
Maamoun Fatfat ◽  
Carla Hankache ◽  
Bassam Osman ◽  
Hala Khalife ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Human Colon ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells
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