scholarly journals Ddb1 Is Essential for the Expansion of CD4+ Helper T Cells by Regulating Cell Cycle Progression and Cell Death

2021 ◽  
Vol 12 ◽  
Author(s):  
Lingtao Yang ◽  
Wei Chen ◽  
Li Li ◽  
Yueyue Xiao ◽  
Shilin Fan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Cell Death ◽  
Cell Cycle Progression ◽  
Helper T Cells ◽  
Genome Maintenance ◽  
Cycle Arrest ◽  
Follicular Helper ◽  
Acute Viral Infection ◽  
M Phase

Follicular helper T (TFH) cells are specialized CD4+ helper T cells that provide help to B cells in humoral immunity. However, the molecular mechanism underlying generation of TFH cells is incompletely understood. Here, we reported that Damage-specific DNA binding protein 1 (Ddb1) was required for expansion of CD4+ helper T cells including TFH and Th1 cells, germinal center response, and antibody response to acute viral infection. Ddb1 deficiency in activated CD4+ T cells resulted in cell cycle arrest at G2-M phase and increased cell death, due to accumulation of DNA damage and hyperactivation of ATM/ATR-Chk1 signaling. Moreover, mice with deletion of both Cul4a and Cul4b in activated CD4+ T cells phenocopied Ddb1-deficient mice, suggesting that E3 ligase-dependent function of Ddb1 was crucial for genome maintenance and helper T-cell generation. Therefore, our results indicate that Ddb1 is an essential positive regulator in the expansion of CD4+ helper T cells.

scholarly journals ER Stress Induces Cell Cycle Arrest at the G2/M Phase Through eIF2α Phosphorylation and GADD45α

2019 ◽  
Vol 20 (24) ◽  
pp. 6309 ◽  
Author(s):  
Duckgue Lee ◽  
Daniel Hokinson ◽  
Soyoung Park ◽  
Rosalie Elvira ◽  
Fedho Kusuma ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Er Stress ◽  
Cell Cycle Arrest ◽  
Cell Cycle Progression ◽  
Growth Arrest ◽  
Cycle Progression ◽  
Eif2α Phosphorylation ◽  
Cycle Arrest ◽  
M Phase

Endoplasmic reticulum (ER) stress is known to influence various cellular functions, including cell cycle progression. Although it is well known how ER stress inhibits cell cycle progression at the G1 phase, the molecular mechanism underlying how ER stress induces G2/M cell cycle arrest remains largely unknown. In this study, we found that ER stress and subsequent induction of the UPR led to cell cycle arrest at the G2/M phase by reducing the amount of cyclin B1. Pharmacological inhibition of the IRE1α or ATF6α signaling did not affect ER stress-induced cell cycle arrest at the G2/M phase. However, when the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation was genetically abrogated, the cell cycle progressed without arresting at the G2/M phase after ER stress. GEO database analysis showed that growth arrest and DNA-damage-inducible protein α (Gadd45α) were induced in an eIF2a phosphorylation-dependent manner, which was confirmed in this study. Knockdown of GADD45α abrogated cell cycle arrest at the G2/M phase upon ER stress. Finally, the cell death caused by ER stress significantly reduced when GADD45α expression was knocked down. In conclusion, GADD45α is a key mediator of ER stress-induced growth arrest via regulation of the G2/M transition and cell death through the eIF2α signaling pathway.

N-(3'-acetyl-8-nitro-2,3-dihydro-1H,3'H-spiro[quinoline-4,2'-[1,3,4]thiadiazol]-5'-yl) acetamides Induced Cell death in MCF-7 cells via G2/M Phase Cell Cycle Arrest

2022 ◽  
Author(s):  
Selvaraj Shyamsivappan ◽  
Raju Vivek ◽  
Thangaraj Suresh ◽  
Palanivel Naveen ◽  
Kaviyarasu Adhigaman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Spectroscopic Studies ◽  
Phase Cell ◽  
X Ray ◽  
Cycle Arrest ◽  
M Phase ◽  
Mcf 7

A progression of new N-(3'-acetyl-8-nitro-2,3-dihydro-1H,3'H-spiro[quinoline-4,2'-[1,3,4]thiadiazol]-5'-yl) acetamide derivatives were synthesized from potent 8-nitro quinoline-thiosemicarbazones. The synthesized compounds were characterized by different spectroscopic studies and single X-ray crystallographic studies. The compounds were...

Novel Thiadiazoline Spiro Quinoline Analogues Induced Cell death in MCF-7 cells via G2/M Phase Cell Cycle Arrest

2021 ◽  
Author(s):  
Selvaraj Shyamsivappan ◽  
Raju Vivek ◽  
Thangaraj Suresh ◽  
Adhigaman Kaviyarasu ◽  
Sundarasamy Amsaveni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Spectroscopic Studies ◽  
Phase Cell ◽  
Quinoline Derivatives ◽  
Cycle Arrest ◽  
M Phase ◽  
Mcf 7

Abstract A progression of novel thiadiazoline spiro quinoline derivatives were synthesized from potent thiadiazoline spiro quinoline derivatives . The synthesized compounds portrayed by different spectroscopic studies and single X-ray crystallographic studies. The compounds were assessed for in vitro anticancer properties towards MCF-7 and HeLa cells. The compounds showed superior inhibition action MCF-7 malignant growth cells. Amongst, the compound 4a showed significant inhibition activity, the cell death mechanism was evaluated by fluorescent staining, and flow cytometry, RT-PCR, and western blot analyses. The in vitro anticancer results revealed that the compound 4a induced apoptosis by inhibition of estrogen receptor alpha (ERα) and G2/M phase cell cycle arrest. The binding affinity of the compounds with ERα and pharmacokinetic properties were confirmed by molecular docking studies.

scholarly journals Antiproliferative Effect of Dihydroxyacetone on Trypanosoma brucei Bloodstream Forms: Cell Cycle Progression, Subcellular Alterations, and Cell Death

2007 ◽  
Vol 51 (11) ◽  
pp. 3960-3968 ◽  
Author(s):  
Néstor L. Uzcátegui ◽  
Didac Carmona-Gutiérrez ◽  
Viola Denninger ◽  
Caroline Schoenfeld ◽  
Florian Lang ◽  
...  
Keyword(s):  
Energy Source ◽  
Cell Cycle ◽  
Trypanosoma Brucei ◽  
Rational Design ◽  
Cell Cycle Progression ◽  
Cell Types ◽  
Cycle Arrest ◽  
Starting Point ◽  
M Phase ◽  
Different Cell Types

ABSTRACT We evaluated the effects of dihydroxyacetone (DHA) on Trypanosoma brucei bloodstream forms. DHA is considered an energy source for many different cell types. T. brucei takes up DHA readily due to the presence of aquaglyceroporins. However, the parasite is unable to use it as a carbon source because of the absence of DHA kinase (DHAK). We could not find a homolog of the relevant gene in the genomic database of T. brucei and have been unable to detect DHAK activity in cell lysates of the parasite, and the parasite died quickly if DHA was the sole energy source in the medium. In addition, during trypanosome cultivation, DHA induced growth inhibition with a 50% inhibitory concentration of about 1 mM, a concentration that is completely innocuous to mammals. DHA caused cell cycle arrest in the G2/M phase of up to 70% at a concentration of 2 mM. Also, DHA-treated parasites showed profound ultrastructural alterations, including an increase of vesicular structures within the cytosol and the presence of multivesicular bodies, myelin-like structures, and autophagy-like vacuoles, as well as a marked disorder of the characteristic mitochondrion structure. Based on the toxicity of DHA for trypanosomes compared with mammals, we consider DHA a starting point for a rational design of new trypanocidal drugs.

Apoptosis Was Induced by Casticin in Acute Myelocytic Leukemia Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3991-3991
Author(s):  
Jie Jin ◽  
Jia-Kun Shen ◽  
Hua-ping Du ◽  
Min Yang ◽  
Yun-Gui Wang
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Death ◽  
Leukemic Cell ◽  
K562 Cells ◽  
Acute Myelocytic Leukemia ◽  
Myelocytic Leukemia ◽  
Cycle Arrest ◽  
M Phase ◽  
Ic50 Values

Abstract Casticin, a component from Vitex rotundifolia wich was widely used as an anti-inflammatory agent in Chinese traditional medicine, was reported to have anti-tumor activities in lung cancer and breast cancer. There are yet no reports on roles against acute myelocytic leukemia (AML). This study aims to elucidate the anti-leukemic activity of casticin on AML cells. We investigated the efficient efficacy and the mechanisms by which casticin triggers cell death in AML cells by analyzing cell cycle perturbations, apoptosis-related marker expression. Cell viability was measured by MTT method; apoptosis and cell cycle arrest were determined by flow cytometry and AV-PI assay. Western blot was performed to measure the apoptosis-related marker. Concentration-dependant cell deaths were observed in AML cell lines including K562, U937 and THP-1, with IC50 values of 24h (hours) being 47.4μM, 67.8μM and 61.7μM, respectively. Time-dependant cell deaths were also observed. At the concentration of 20μM casticin, 45.7%, 76.1% and 80.9% of K562 cells were inhibited at 24h, 48h and 72h, respectively; 24.7%, 30% and 61% of U937 cells were inhibited at 24h, 48h and 72h, respectively; while for THP-1, 29%, 41.8% and 53.9% were inhibited at 24h, 48h and 72h, respectively. Apoptosis was found using AV-PI staining by flow cytometry analysis. We observed an obvious G2/M phase increase prolongation in casticin treated K562 cells. BThe distribitions of G2/M phase were 2.9%, 33.6%, 75.3%, 54.9%, 29.7% and 27.0% in K562 cells after treated by 20μM casticin for 0h, 6h, 12h, 24h, 36h and 48h, respectively. Furthermore, apoptosis-related proteins, PARP and caspase 3, were cleaved in casticin treated K562 cells. Taken together, these results demonstrated that casticin can induce leukemic cell death through apoptosis, suggesting that casticin could be a promising therapeutic agent against acute myeloid leukemia.

Saponins from soy bean and mung bean inhibit the antigen specific activation of helper T cells by blocking cell cycle progression

2012 ◽  
Vol 35 (2) ◽  
pp. 165-173 ◽  
Author(s):  
Suk Jun Lee ◽  
Joonbeom Bae ◽  
Sunhee Kim ◽  
Seonah Jeong ◽  
Chang-Yong Choi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Mung Bean ◽  
Cell Cycle Progression ◽  
Helper T Cells ◽  
Cycle Progression

scholarly journals Therapeutic targeting PLK1 by ON-01910.Na is effective in local treatment of retinoblastoma

2021 ◽  
Author(s):  
Huan Ma ◽  
Cong Nie ◽  
Ying Chen ◽  
Jinmiao Li ◽  
Yanjie Xie ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Cell Cycle Progression ◽  
Structural Integrity ◽  
Apoptotic Cell ◽  
Disease Model ◽  
Local Treatment ◽  
Three Dimensional ◽  
Cycle Arrest

Cell cycle deregulation is involved in pathogenesis of many cancers, and often associated with protein kinase aberrations, including the polo-like kinase 1 (PLK1). Wehereby used retinoblastoma, an intraocular malignancy that lacks targeted therapy, as a disease model and set out to reveal targetability of PLK1 with a small molecularinhibitor ON-01910.Na. First, transcriptomic analysis on patient retinoblastoma tissues suggested that cell cycle progression was deregulated and confirmed that PLK1pathway was upregulated. Next, antitumor activity of ON-01910.Na was investigated inboth cellular and animal levels. Cytotoxicity induced by ON-01910.Na was tumor-specific and dose-dependent in retinoblastoma cells, whilst non-tumor cells wereminimally affected. In three-dimensional culture, ON-01910.Na demonstrated efficient drug-penetrability with multilayer cell death. Post-treatment transcriptomic findingsrevealed that cell cycle arrest and MAPK cascade activation were induced following PLK1 inhibition, and eventually result in apoptotic cell death. In Balb/c nude mice, a safe threshold of 0.8 nmol intravitreal dosage of ON-01910.Na was established for intraocular safety, which was demonstrated by structural integrity and functional preservation. Furthermore, intraocular and subcutaneous xenograft were significantlyreduced with ON-01910.Na treatments. For the first time, we demonstrated targetability of PLK1 in retinoblastoma by efficiently causing cell cycle arrest and apoptosis. Ourstudy is supportive that local treatment of ON-01910.Na may be a novel, effectivemodality benefiting patients with PLK1-aberrant tumors.

HSP27 regulates p53 transcriptional activity in doxorubicin-treated fibroblasts and cardiac H9c2 cells: p21 upregulation and G2/M phase cell cycle arrest

2008 ◽  
Vol 294 (4) ◽  
pp. H1736-H1744 ◽  
Author(s):  
C. D. Venkatakrishnan ◽  
Kathy Dunsmore ◽  
Hector Wong ◽  
Sashwathi Roy ◽  
Chandan K. Sen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Heat Shock ◽  
Cell Cycle Arrest ◽  
Transcriptional Activity ◽  
Neonatal Rat ◽  
Phase Cell ◽  
H9c2 Cells ◽  
Cycle Arrest ◽  
M Phase

Treatment of cancer patients with anthracyclin-based chemotherapeutic drugs induces congestive heart failure by a mechanism involving p53. However, it is not known how p53 aggravates doxorubicin (Dox)-induced toxicity in the heart. On the basis of in vitro acute toxicity assay using heat shock factor-1 (HSF-1) wild-type (HSF-1+/+) and HSF-1-knockout (HSF-1−/−) mouse embryonic fibroblasts and neonatal rat cardiomyocyte-derived H9c2 cells, we demonstrate a novel mechanism whereby heat shock protein 27 (HSP27) regulates transcriptional activity of p53 in Dox-treated cells. Inhibition of p53 by pifithrin-α (PFT-α) provided different levels of protection from Dox that correlate with HSP27 levels in these cells. In HSF-1+/+ cells, PFT-α attenuated Dox-induced toxicity. However, in HSF-1−/− cells (which express a very low level of HSP27 compared with HSF-1+/+ cells), there was no such attenuation, indicating an important role of HSP27 in p53-dependent cell death. On the other hand, immunoprecipitation of p53 was found to coimmunoprecipitate HSP27 and vice versa (confirmed by Western blotting and matrix-assisted laser desorption/ionization time of flight), demonstrating HSP27 binding to p53 in Dox-treated cells. Moreover, upregulation of p21 was observed in HSF-1+/+ and H9c2 cells, indicating that HSP27 binding transactivates p53 and enhances transcription of p21 in response to Dox treatment. Further analysis with flow cytometry showed that increased expression of p21 results in G2/M phase cell cycle arrest in Dox-treated cells. Overall, HSP27 binding to p53 attenuated the cellular toxicity by upregulating p21 and prevented cell death.

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