NB1011 induces Ser15 phosphorylation of p53 and activates the G2/M checkpoint

Dellinger, Ryan W.; Karjian, Patricia L.; Neuteboom, Saskia

doi:10.1097/00001813-200307000-00011

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…In G2/M arrest, cdc2, the kinase required for entry into mitosis, is inhibited by various mechanisms. p21 and 14-3-3 σ , which are transcriptional targets of p53, play key roles in inhibiting cdc2 activity (Taylor and Stark, 2001; Dellinger et al , 2003). 14-3-3 σ has been reported to be a critical regulator of the G2/M checkpoint in both p53 wild-type and mutant PC-3 cancer cells (Han et al , 2006).…”

Section: Discussionmentioning

confidence: 99%

Enhancement of radiosensitivity by a unique novel NF-κB inhibitor, DHMEQ, in prostate cancer

et al. 2012

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Background:Inducible activation of nuclear factor (NF)-κB is one of the principal mechanisms through which resistant prostate cancer cells are protected from radiotherapy. We hypothesised that inactivation of inducible NF-κB with a novel NF-κB inhibitor, DHMEQ, would increase the therapeutic effects of radiotherapy.Methods:PC-3 and LNCaP cells were exposed to irradiation and/or DHMEQ. Cell viability, cell cycle analysis, western blotting assay, and NF-κB activity were measured. The antitumour effect of irradiation combined with DHMEQ in vivo was also assessed.Results:The combination of DHMEQ with irradiation resulted in cell growth inhibition and G2/M arrest relative to treatment with irradiation alone. Inducible NF-κB activity by irradiation was inhibited by DHMEQ treatment. The expression of p53 and p21 in LNCaP, and of 14-3-3σ in PC-3 cells, was increased in the combination treatment. In the in vivo study, 64 days after the start of treatment, tumour size was 85.1%, 77.1%, and 64.7% smaller in the combination treatment group than that of the untreated control, DHMEQ-treated alone, and irradiation alone groups, respectively.Conclusion:Blockade of NF-κB activity induced by radiation with DHMEQ could overcome radio-resistant responses and may become a new therapeutic modality for treating prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Enhancement of radiosensitivity by a unique novel NF-κB inhibitor, DHMEQ, in prostate cancer

et al. 2012

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“…Further studies into the mechanism of action of thymectacin suggested the involvement of the tumour suppressor p53 and the activation of the G2/M checkpoint eventually contributing to cell cycle arrest. 45 Phase I clinical trials of thymectacin dosed intravenously in patients with advanced colorectal cancer that failed 5-FU treatment was initiated. Initial results using doses ranging from 200 mg/kg to 1250 mg/kg showed that thymectacin was well tolerated and a number of patients achieved a stable disease state.…”

Section: Stampidine and Thymectacinmentioning

confidence: 99%

“…This pointed to a unique nucleotide-mediated labeling of proteins that causes cytotoxicity. Further studies into the mechanism of action of thymectacin suggested the involvement of the tumor suppressor p53 and the activation of the G2/M checkpoint eventually contributing to cell cycle arrest …”

Section: Pronucleotide Clinical Candidatesmentioning

confidence: 99%

Nucleoside Phosphate and Phosphonate Prodrug Clinical Candidates

et al. 2016

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Nucleoside monophosphates and monophosphonates have been known for a long time to exert favorable pharmacological effects upon intracellular delivery. However, their development as drug molecules has been hindered by the inherent poor druglike properties of the monophosphate and monophosphonate groups. These include inefficient cellular uptake and poor in vivo stability, with this latter drawback being most relevant to monophosphates than monophosphonates. To address these limitations, numerous monophosphate and monophosphonate prodrug strategies have been developed and applied in the discovery of nucleoside monophosphate and monophosphonate prodrugs that can treat viral infections and cancer. The approval of sofosbuvir, a nucleoside monophosphate prodrug, highlighted the success to be had by employing these prodrug technologies in the discovery of nucleotide therapeutics. In this Miniperspective, we discuss the different key monophosphate and monophosphonate nucleoside prodrugs that entered clinical development, some of which may in the future be approved to treat various human diseases.

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Knockdown of IARS2 suppressed growth of gastric cancer cells by regulating the phosphorylation of cell cycle-related proteins

et al. 2017

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The purpose of the article is to investigate the role of IARS2 in proliferation, apoptosis, and cell cycle of gastric cancer (GC) cells in vitro. The IARS2-shRNA lentiviral vector was established and used to infect the GC cell line AGS. qRT-PCR and Western blot were employed to determine the efficiency of IARS2 knockdown. The effects of IARS2 knockdown on cell proliferation, cell clone formation, and cell cycle were assessed by MTT assay, colony formation assay, and flow cytometer analysis, respectively. Finally, a PathScan Antibody Array Kit was used to detect the expression levels of cell cycle-related proteins after IARS2 knockdown in AGS cells to elucidate the underlying mechanisms. Compared with negative control group, IARS2 was significantly knocked down by transfection with lentivirus encoding shRNA of IARS2 in AGS cells. IARS2 knockdown significantly inhibited the proliferation and colony formation ability and induced cycle arrest at G2/M phase of AGS cells. IARS2 knockdown significantly decreased the expression levels of phosphorylation of (p-Smad2), p-SAPK/JUK, cleavage-Caspase-7, and p-TAK1, but increased the expression levels of p-53 and cleavage-PARP in AGS cells compared to shCtrl group. We demonstrated that IARS2 knockdown inhibits proliferation, suppresses colony formation, and causes cell cycle arrest in AGS cells. We also found that IARS2 regulates key molecules of cell apoptosis-related signaling pathway.

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NB1011 induces Ser15 phosphorylation of p53 and activates the G2/M checkpoint

Cited by 5 publications

References 25 publications

Enhancement of radiosensitivity by a unique novel NF-κB inhibitor, DHMEQ, in prostate cancer

Enhancement of radiosensitivity by a unique novel NF-κB inhibitor, DHMEQ, in prostate cancer

Nucleoside Phosphate and Phosphonate Prodrug Clinical Candidates

Knockdown of IARS2 suppressed growth of gastric cancer cells by regulating the phosphorylation of cell cycle-related proteins

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