Effect of dihydroarteminin combined with siRNA targeting Notch1 on Notch1/c-Myc signaling in T-cell lymphoma cells

Huo, Lanfen; Wei, Wuran; Wu, Shao-Ling; Zhao, Xiangxuan; Zhao, Chunting; Zhao, Hongguo; Sun, Lingjie

doi:10.3892/etm.2018.5784

Cited by 3 publications

(2 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because Notch1 is a critical oncogene that drives proliferation of T-ALL cells and it is required for proliferation of T-ALL cell lines including Jurkat cells 36,37 , we evaluated these compounds in Western blots to determine the effect on Notch1 expression. Of this panel, only DGBP completely and dose-dependently decreased Notch1 protein expression and levels of the Notch1 NICD in both Jurkat (Fig.…”

Section: Resultsmentioning

confidence: 99%

Regulation of the Notch-ATM-abl axis by geranylgeranyl diphosphate synthase inhibition

Agabiti

Dong

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

Notch proteins drive oncogenesis of many cancers, most prominently T-cell acute lymphoblastic leukemia (T-ALL). Because geranylgeranylated Rab proteins regulate Notch processing, we hypothesized that inhibition of geranylgeranyl diphosphate synthase (GGDPS) would impair Notch processing and reduce viability of T-ALL cells that express Notch. Here, we show that GGDPS inhibition reduces Notch1 expression and impairs the proliferation of T-ALL cells. GGDPS inhibition also reduces Rab7 membrane association and depletes Notch1 mRNA. GGDPS inhibition increases phosphorylation of histone H2A.X, and inhibitors of ataxia telangiectasia-mutated kinase (ATM) mitigate GGDPS inhibitor-induced apoptosis. GGDPS inhibition also influences c-abl activity downstream of caspases, and inhibitors of these enzymes prevent GGDPS inhibitor-induced apoptosis. Surprisingly, induction of apoptosis by GGDPS inhibition is reduced by co-treatment with γ-secretase inhibitors. While inhibitors of γ-secretase deplete one specific form of the Notch1 intracellular domain (NICD), they also increase Notch1 mRNA expression and increase alternate forms of Notch1 protein expression in cells treated with a GGDPS inhibitor. Furthermore, inhibitors of γ-secretase and ATM increase Notch1 mRNA stability independent of GGDPS inhibition. These results provide a model by which T-ALL cells use Notch1 to avoid DNA-damage-induced apoptosis, and can be overcome by inhibition of GGDPS through effects on Notch1 expression and its subsequent response.

show abstract

Section: Resultsmentioning

confidence: 99%

Regulation of the Notch-ATM-abl axis by geranylgeranyl diphosphate synthase inhibition

Agabiti

Dong

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…As a zinc finger transcription factor, CTCF was first identified as a transcriptional repressor of the chicken Myc gene. However, later studies revealed that CTCF is involved in Myc transcription regulation by multiple mechanisms with cell type- and cell physiology-specific mechanisms [ 37 , 38 , 43 , 44 ]. Our current research suggests that the interaction between Tet1 and CTCF contributes to Myc expression control via the specific cis-element “site A”.…”

Section: Discussionmentioning

confidence: 99%

Induced hepatic stem cells maintain self-renewal through the high expression of Myc coregulated by TET1 and CTCF

Wang

Ding

et al. 2022

Cell Biosci

View full text Add to dashboard Cite

Background Induced hepatic stem cells (iHepSCs) with the capacities of self-renewal and bidifferentiation into hepatocytes and cholangiocytes were generated from mouse embryonic fibroblasts (MEFs) by lineage reprogramming in our previous research. However, the mechanism of iHepSC self-renewal has not been elucidated. Active demethylation regulated by Tet1 plays an important role in the self-renewal of stem cells, including pluripotent stem cells and adult stem cells. Here, we investigated the role and mechanism of Tet1-regulated demethylation in the self-renewal of iHepSCs. Methods The methylation levels and the expression of Tet1 in iHepSCs and MEFs were analyzed by immunofluorescent staining, quantitative reverse transcription PCR and western blotting. Then, the effects of Tet1 knockdown on the proliferation and self-renewal of iHepSCs were analyzed by CCK8, colony formation, and sphere formation assays. The mechanism by which Tet1 regulates the self-renewal of iHepSCs was investigated by chromatin immunoprecipitation, bisulfite sequence PCR, and methylation-sensitive restriction endonuclease-PCR. Results The high level of 5hmC and the low level of 5mC in iHepSCs were accompanied by high expression of Tet1. After Tet1 expression was knocked down by shRNA in iHepSCs, the proliferation and self-renewal capacities were inhibited, and the expression of Myc was also decreased. The higher expression level of Myc in iHepSCs maintained its self-renewal and was regulated by Tet1, which directly binds to CBS-1 and site A regions of the Myc promoter and demethylates the CpG cytosine. In addition, CTCF also binds to the CBS-1 and site A regions of the Myc promoter and regulates Myc expression along with TET1. Conclusion The self-renewal of iHepSCs was maintained by the higher expression of Myc, which was coregulated by TET1 and CTCF. This study may provide new insights into the self-renewal of stem cells, which can promote the research and application of ‘reprogrammed’ stem cells.

show abstract

Combination Therapies of Artemisinin and its Derivatives as a Viable Approach for Future Cancer Treatment

Kumar

Yadav

Khair

et al. 2019

CPD

View full text Add to dashboard Cite

Background: Many anticancer drugs have been developed for clinical usage till now, but the major problem is the development of drug-resistance over a period of time in the treatment of cancer. Anticancer drugs produce huge adverse effects, ultimately leading to death of the patient. Researchers have been focusing on the development of novel molecules with higher efficacy and lower toxicity; the anti-malarial drug artemisinin and its derivatives have exhibited cytotoxic effects. Methods: We have done extensive literature search for artemisinin for its new role as anti-cancer agent for future treatment. Last two decades papers were referred for deep understanding to strengthen its role. Results: Literature shows changes at 9, 10 position in the artemisinin structure produces anticancer activity. Artemisinin shows anticancer activity in leukemia, hepatocellular carcinoma, colorectal and breast cancer cell lines. Artemisinin and its derivatives have been studied as combination therapy with several synthetic compounds, RNA interfaces, recombinant proteins and antibodies etc., for synergizing the effect of these drugs. They produce an anticancer effect by causing cell cycle arrest, regulating signaling in apoptosis, angiogenesis and cytotoxicity activity on the steroid receptors. Many novel formulations of artemisinin are being developed in the form of carbon nanotubes, polymer-coated drug particles, etc., for delivering artemisinin, since it has poor water/ oil solubility and is chemically unstable. Conclusion: We have summarize the combination therapies of artemisinin and its derivatives with other anticancer drugs and also focussed on recent developments of different drug delivery systems in the last 10 years. Various reports and clinical trials of artemisinin type drugs indicated selective cytotoxicity along with minimal toxicity thus projecting them as promising anti-cancer agents in future cancer therapies.

show abstract

Effect of dihydroarteminin combined with siRNA targeting Notch1 on Notch1/c-Myc signaling in T-cell lymphoma cells

Cited by 3 publications

References 30 publications

Regulation of the Notch-ATM-abl axis by geranylgeranyl diphosphate synthase inhibition

Regulation of the Notch-ATM-abl axis by geranylgeranyl diphosphate synthase inhibition

Induced hepatic stem cells maintain self-renewal through the high expression of Myc coregulated by TET1 and CTCF

Combination Therapies of Artemisinin and its Derivatives as a Viable Approach for Future Cancer Treatment

Contact Info

Product

Resources

About