Widdrol activates DNA damage checkpoint through the signaling Chk2–p53–Cdc25A–p21–MCM4 pathway in HT29 cells

Yun, Hee Jung; Hyun, Sook Kyung; Park, Jung Ha; Kim, Byung Woo; Kwon, Hyun Ju

doi:10.1007/s11010-011-1180-z

Cited by 25 publications

(18 citation statements)

References 25 publications

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“…On the other hand, several different HDACIs have been shown to increase expression of p21 in several different tumor cell lines (42,43). CHEK2 also has been shown to activate p21 (44). In our experiments, we observed a modest induction of p21 upon treatment with CHEK2i and, in agreement with previous reports, a very significant increase in p21 levels when cells were treated with the HDACI AR42.…”

Section: Discussionsupporting

confidence: 92%

Efficacy of Combined Histone Deacetylase and Checkpoint Kinase Inhibition in a Preclinical Model of Human Burkitt Lymphoma

Kong

Barisone

Sidhu

et al. 2015

Mol Med

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Checkpoint kinase inhibition has been studied as a way of enhancing the effectiveness of DNA-damaging agents. More recently, histone deacetylase inhibitors have shown efficacy in several cancers, including non-Hodgkin lymphoma. To evaluate the effectiveness of this combination for the treatment of lymphoma, we examined the combination of AR42, a histone deacetylase inhibitor, and checkpoint kinase 2 (CHEK2) inhibitor II in vitro and in vivo. The combination resulted in up to 10-fold increase in potency in five Burkitt lymphoma cell lines when compared with either drug alone. Both drugs inhibited tumor progression in xenograft models, but the combination was more effective than either agent alone, resulting in regression of established tumors. No toxicity was observed. These results suggest that the combination of histone deacetylase inhibition and checkpoint kinase inhibition represent an effective and nontoxic treatment option that should be further explored in preclinical and clinical studies. online address: http://www.molmed.org

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Section: Discussionsupporting

confidence: 92%

Efficacy of Combined Histone Deacetylase and Checkpoint Kinase Inhibition in a Preclinical Model of Human Burkitt Lymphoma

Kong

Barisone

Sidhu

et al. 2015

Mol Med

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“…To further clarify the molecular mechanisms by which atrazine affects cell cycle and apoptosis in RM1 cells, RT-PCR and western blot analyses were employed to detect the mRNA and protein levels of factors related to cell cycle and apoptosis. The cell cycle has many checkpoints, and p53 and p21 play important roles in cell cycle arrest through the Chk2-p53-Cdc25A-p21-MCM4 signaling pathway, and finally induce G1 cell cycle arrest; overexpression of p21 induces cell cycle arrest (23). In this study, p53 and p21 mRNA and protein levels were downregulated in vitro and in vivo after exposure to atrazine, which indicated that atrazine inhibits cell cycle arrest.…”

Section: Discussionmentioning

confidence: 53%

Atrazine promotes RM1 prostate cancer cell proliferation by activating STAT3 signaling

Tian

et al. 2016

International Journal of Oncology

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Atrazine, a widely used pesticide, is frequently detected in soil and surface water, which alarms epidemiologists and medical professionals because of its potential deleterious effects on health. Indeed, atrazine is a potent endocrine disruptor that increases aromatase expression in some human cancer cell lines. Both animal and human studies have suggested that atrazine is possibly carcinogenic, although discrepant results have been reported. In this study, RM1 cells were used to explore the atrazine effects on prostate cancer. Proliferation, migration and invasion of RM1 cells were assessed by colony formation, wound-healing and invasion assays, respectively, after in vitro exposure to atrazine. In addition, an RM1 cell xenograft model was generated to evaluate the effects of atrazine in vivo. To explore the molecular mechanisms, qRT‑PCR, immunohistochemistry, and western blot analyses were employed to detect mRNA and protein levels of STAT3 signaling and cell cycle related proteins, including p53, p21, cyclin B1 and cyclin D1. Interestingly, RM1 cell proliferation was increased after treatment with atrazine, concomitantly with STAT3 signaling activation. These results suggest that atrazine promotes RM1 cell growth in vitro and in vivo by activating STAT3 signaling.

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“…Some odors can induce the phosphorylation of AMP-activated protein kinase (AMPK), leading to cell cycle arrest and apoptosis in a colon cancer cell line [34]. Linalool is capable of mediating antiproliferative effects in melanoma cells [35].…”

Section: Discussionmentioning

confidence: 99%

Activation of odorant receptor in colorectal cancer cells leads to inhibition of cell proliferation and apoptosis

et al. 2017

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The analysis and functional characterization of ectopically expressed human olfactory receptors (ORs) is becoming increasingly important, as many ORs have been identified in several healthy and cancerous tissues. OR activation has been demonstrated to have influence on cancer cell growth and progression. Here, ORs were identified using RNA-Seq analyses and RT-PCR. We demonstrated the OR protein localization in HCT116 cells using immunocytochemistry (IHC). In order to analyze the physiological role of OR51B4, we deorphanized the receptor by the use of CRE-Luciferase assays, conducted calcium imaging experiments as well as scratch- and proliferation assays. Furthermore, western blot analyses revealed the involvement of different protein kinases in the ligand-dependent signaling pathway. Receptor knockdown via shRNA was used to analyze the involvement of OR51B4.We identified OR51B4, which is highly expressed in the colon cancer cell line HCT116 and in native human colon cancer tissues. We deorphanized the receptor and identified Troenan as an effective ligand. Troenan stimulation of HCT116 cells has anti-proliferative, anti-migratory and pro-apoptotic effects, mediated by changes in the intracellular calcium level upon PLC activation. These effects cause changes in the phosphorylation levels of p38, mTor and Akt kinases. Knockdown of the receptor via shRNA confirmed the involvement of OR51B4.This study emphasizes the importance of ectopically expressed ORs in the therapy for several diseases. The findings provide the basis for alternative treatments of colorectal cancer.

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Widdrol activates DNA damage checkpoint through the signaling Chk2–p53–Cdc25A–p21–MCM4 pathway in HT29 cells

Cited by 25 publications

References 25 publications

Efficacy of Combined Histone Deacetylase and Checkpoint Kinase Inhibition in a Preclinical Model of Human Burkitt Lymphoma

Efficacy of Combined Histone Deacetylase and Checkpoint Kinase Inhibition in a Preclinical Model of Human Burkitt Lymphoma

Atrazine promotes RM1 prostate cancer cell proliferation by activating STAT3 signaling

Activation of odorant receptor in colorectal cancer cells leads to inhibition of cell proliferation and apoptosis

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