scholarly journals Acrolein-Derived DNA Adduct Formation in Human Colon Cancer Cells: Its Role in Apoptosis Induction by Docosahexaenoic Acid

2009 ◽  
Vol 22 (5) ◽  
pp. 798-806 ◽  
Author(s):  
Jishen Pan ◽  
Jessica Keffer ◽  
Armaghan Emami ◽  
Xiaoyue Ma ◽  
Renny Lan ◽  
...  
2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Kyeong-Ah Jung ◽  
Mi-Kyoung Kwak

Nuclear factor erythroid 2-related factor 2 (NRF2) is the transcription factor that regulates an array of antioxidant/detoxifying genes for cellular defense. The conformational changes of Kelch-like ECH-associated protein 1 (KEAP1), a cytosolic repressor protein of NRF2, by various stimuli result in NRF2 liberation and accumulation in the nucleus. In the present study, we aimed to investigate the effect ofKEAP1knockdown on NRF2 target gene expression and its toxicological implication using human colon cancer cells. The stableKEAP1-knockdown HT29 cells exhibit elevated levels of NRF2 and its target gene expressions. In particular, the mRNA levels of aldo-keto reductases (AKR1C1, 1C2, 1C3, 1B1, and 1B10) were substantially increased inKEAP1silenced HT29 cells. These differential AKRs expressions appear to contribute to protection against oxidative stress. TheKEAP1-knockdown cells were relatively more resistant to hydrogen peroxide (H2O2) and 4-hydroxynonenal (4HNE) compared to the control cells. Accordantly, we observed accumulation of 4HNE protein adducts in H2O2- or 4HNE-treated control cells, whereasKEAP1-knockdown cells did not increase adduct formation. The treatment ofKEAP1-silenced cells with AKR1C inhibitor flufenamic acid increased 4HNE-induced cellular toxicity and protein adduct formation. Taken together, these results indicate that AKRs, which are NRF2-dependent highly inducible gene clusters, play a role in NRF2-mediated cytoprotection against lipid peroxide toxicity.


2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Chi-Tai Yeh ◽  
Chih-Jung Yao ◽  
Jiann-Long Yan ◽  
Shuang-En Chuang ◽  
Liang-Ming Lee ◽  
...  

Aberrant activation of Wnt/β-catenin signaling plays an important role in the development of colon cancer. HS7 is an active fraction extracted fromTaiwanofungus camphoratus, which had been widely used as complementary medicine for Taiwan cancer patients in the past decades. In this study, we demonstrated the effects of HS7 on the growth inhibition, apoptosis induction, and Wnt/β-catenin signaling suppression in human colon cancer cells. HS7 significantly inhibited proliferation of HT29, HCT116, and SW480 colon cancer cells in a dose- and time-dependent manner. The apoptosis induction was evidenced by DNA fragmentation and subG1 accumulation, which was associated with increased Bax/Bcl-2 ratio, activation of caspase-3 and cleavage of PARP. By using Tcf-dependent luciferase activity assay, HS7 was found to inhibit theβ-catenin/Tcf transcriptional activities. In addition, HS7 strongly suppressed the binding of Tcf complexes to its DNA-binding site shown in electrophoretic mobility shift assay. This inhibition was further confirmed by the decreased protein levels of Tcf-4 andβ-catenin. Theβ-catenin/Tcf downstream target genes, such assurvivin,c-myc,cyclin D1,MMP7, andMT1-MMPinvolved in apoptosis, invasion, and angiogenesis were also diminished as well. These results indicate thatTaiwanofungus camphoratusmay provide a benefit as integrative medicine for the treatment of colon cancer.


2012 ◽  
Vol 75 (11) ◽  
pp. 1896-1902 ◽  
Author(s):  
Olga Wesołowska ◽  
Jerzy Wiśniewski ◽  
Kamila Środa-Pomianek ◽  
Aleksandra Bielawska-Pohl ◽  
Maria Paprocka ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A493-A493
Author(s):  
J HARDWICK ◽  
G VANDENBRINK ◽  
S VANDEVENTER ◽  
M PEPPELENBOSCH

Sign in / Sign up

Export Citation Format

Share Document