Ethanol metabolism activates cell cycle checkpoint kinase, Chk2

Clemens, Dahn L.; Schneider, Katrina J.; Nuss, Robert F.

doi:10.1016/j.alcohol.2011.07.005

Cited by 9 publications

(6 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Benzo(a)pyrene diol epoxide, present in tobacco smoke, is suggested to increase ATM expression in premalignant and malignant esophageal tissues . Ethanol metabolism increased the active forms of ATM in hepatocyte . Low‐dose arecoline (15.5 μg/mL) treatment enhances the genotoxicity of benzo(a)pyrene by suppressing DNA repair in HEp‐2 cells .…”

Section: Discussionmentioning

confidence: 99%

Arecoline‐regulated ataxia telangiectasia mutated expression level in oral cancer progression

Chen

Lai

et al. 2019

Head & Neck

View full text Add to dashboard Cite

Background Ataxia telangiectasia mutated (ATM) regulates DNA repair and cell cycle. The present study analyzed arecoline‐induced ATM expression during oral cancer progression. Methods In vitro studies were performed using oral squamous cell carcinoma (OSCC) cell lines treated with arecoline to analyze cell response and ATM regulation. in vivo studies were performed using immunohistochemistry to detect ATM expression in normal, oral potentially malignant disorder (OPMD), and OSCC tissues. Results Low‐dose arecoline induced cell proliferation, ATM promoter activity, and DNA repair. High‐dose arecoline induced cell cycle arrest, apoptosis, and DNA damage. ATM was overexpressed in OPMD tissues but was downregulated in OSCC tissues. ATM expression level was associated with the risk of developing dysplasia, buccal‐OSCC, and with OSCC survival rate. Conclusion High ATM expression helps DNA repair mechanisms to maintain the cells in the OPMD stage, but low ATM expression causes DNA damage accumulation to increase cell malignancy.

show abstract

Section: Discussionmentioning

confidence: 99%

Arecoline‐regulated ataxia telangiectasia mutated expression level in oral cancer progression

Chen

Lai

et al. 2019

Head & Neck

View full text Add to dashboard Cite

show abstract

“…The G2/M checkpoint, which functions as cells mitosis stunner, is considered to be a conspicuous target for anticancer drugs. There are many essential proteins involved in G2/M phase transformation, including cyclin B1, cdc2, and p27 13 . In addition, Apoptosis and autophagy are known as a major cellular molecular mechanism to regulate cancer progression and maintain the homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Propranolol induced apoptosis and autophagy via the ROS/JNK signaling pathway in Human Ovarian Cancer

Zhao¹,

Fan²,

Shi³

et al. 2020

J. Cancer

View full text Add to dashboard Cite

Propranolol has a significant anti-cancer effect towards various cancers. Our study aimed at investigating the underlying mechanism of Propranolol's therapeutic effect towards ovarian cancer. Specifically, Propranolol significantly reduced the viability of human ovarian cancer cell lines SKOV-3 and A2780 in a dose-and time-dependent manner. Flow cytometry analysis revealed that Propranolol induced the cell cycle arrest at G2/M phase therefore leading to apoptosis. Moreover, autophagy inhibitor 3-MA markedly enhanced the Propranolol-induced apoptosis. In addition, reactive oxygen species (ROS) increased dramatically after Propranolol treatment and Propranolol activated the phosphorylation of JNK. What is more, p38 inhibitor SB203580 and JNK inhibitor SP600125 attenuated the upregulated expression of LC3-II and cleaved-caspase-3 by the effect of Propranolol. ROS exclusive inhibitor antioxidant N-acetyl cysteine (NAC) weakens the phosphorylation of JNK proteins induced by Propranolol. In summary, these results suggested that Propranolol induced cell apoptosis and protective autophagy through the ROS/JNK signaling pathway in human ovarian cancer cells.

show abstract

“…Detection of these adducts by the cell activates the checkpoint kinases and arrests the cell cycle progression. In previous studies, we demonstrated that ethanol metabolism by VA-13 cells activates ataxia-telangiectasia mutated (ATM), which in turn activates the checkpoint kinase Chk2 [ 15 ]. Chk2 can phosphorylate Cdc25c the phosphatase that activates Cdc2.…”

Section: Discussionmentioning

confidence: 99%

“…This impairment in cellular replication is, at least partially, the result of a G2/M cell cycle arrest. Furthermore, this G2/M cell cycle arrest is mediated, at least in part, by the activation of cell cycle check point kinases and the accumulation of the cyclin dependent kinase, Cdc2, in the inactive, phosphorylated form [ 1 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

The Involvement of Acetaldehyde in Ethanol-Induced Cell Cycle Impairment

et al. 2016

View full text Add to dashboard Cite

Background: Hepatocytes metabolize the vast majority of ingested ethanol. This metabolic activity results in hepatic toxicity and impairs the ability of hepatocytes to replicate. Previous work by our group has shown that ethanol metabolism results in a G2/M cell cycle arrest. The intent of these studies was to discern the roles of acetaldehyde and reactive oxygen, two of the major by-products of ethanol metabolism, in the G2/M cell cycle arrest. Methods: To investigate the role of ethanol metabolites in the cell cycle arrest, VA-13 and VL-17A cells were used. These are recombinant Hep G2 cells that express alcohol dehydrogenase or alcohol dehydrogenase and cytochrome P450 2E1, respectively. Cells were cultured with or without ethanol, lacking or containing the antioxidants N-acetylcysteine (NAC) or trolox, for three days. Cellular accumulation was monitored by the DNA content of the cultures. The accumulation of the cyclin-dependent kinase, Cdc2 in the inactive phosphorylated form (p-Cdc2) and the cyclin-dependent kinase inhibitor p21 were determined by immunoblot analysis. Results: Cultures maintained in the presence of ethanol demonstrated a G2/M cell cycle arrest that was associated with a reduction in DNA content and increased levels of p-Cdc2 and p21, compared with cells cultured in its absence. Inclusion of antioxidants in the ethanol containing media was unable to rescue the cells from the cell cycle arrest or these ethanol metabolism-mediated effects. Additionally, culturing the cells in the presence of acetaldehyde alone resulted in increased levels of p-Cdc2 and p21. Conclusions: Acetaldehyde produced during ethanol oxidation has a major role in the ethanol metabolism-mediated G2/M cell cycle arrest, and the concurrent accumulation of p21 and p-Cdc2. Although reactive oxygen species are thought to have a significant role in ethanol-induced hepatocellular damage, they may have a less important role in the inability of hepatocytes to replace dead or damaged cells.

show abstract

Ethanol metabolism activates cell cycle checkpoint kinase, Chk2

Cited by 9 publications

References 40 publications

Arecoline‐regulated ataxia telangiectasia mutated expression level in oral cancer progression

Arecoline‐regulated ataxia telangiectasia mutated expression level in oral cancer progression

Propranolol induced apoptosis and autophagy via the ROS/JNK signaling pathway in Human Ovarian Cancer

The Involvement of Acetaldehyde in Ethanol-Induced Cell Cycle Impairment

Contact Info

Product

Resources

About