Apoptotic and cell cycle response to homoharringtonine and harringtonine in wild and mutant p53 hepatocarcinoma cells

2020 ◽  
Vol 39 (10) ◽  
pp. 1405-1416
Author(s):  
DP Franco ◽  
BI de Biazi ◽  
TA Zanetti ◽  
LA Marques ◽  
LVA de Lima ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Er Stress ◽  
Mrna Expression ◽  
Cell Cycle Control ◽  
Membrane Integrity ◽  
Cycle Phase ◽  
Mutant P53 ◽  
Relative Expression ◽  
Stress Genes ◽  
Tnf Induction

This study aimed to evaluate the modes of action of harringtonine (HT) and homoharringtonine (HHT) alkaloids in cell with wild (HepG2/C3A) and mutant p53 (HuH-7.5). We performed assays for cytotoxicity, genotoxicity, induction of apoptosis, cell cycle phase, and membrane integrity. Obtained data were compared with the relative expression of mRNA of genes related to proliferation, apoptosis, cell cycle control, metabolism of xenobiotics, and reticulum endoplasmic stress. The relative expression of the genes showed an increase in apoptosis-inducing mRNAs, such as TNF and BBC3, as well as a reduction in BCL2 and BAK. The mRNAs of CYP2E1 and CYP2C19 xenobiotic metabolism genes increased in both lineages, while CYP3A4 increased only in the HuH-7.5 lineage. The mRNA expression of endoplasmic reticulum (ER) stress genes ( ERN1 and EIF2AK3) was shown to increase in HHT and HT treatments. A similar increase was recorded in the mRNA expression of the TRAF2 gene. The changes observed in this study support the hypothesis that ER stress was more strongly associated with TNF induction, causing cell death by apoptosis in p53 mutant cells. This result with wild and mutant p53 cells may have clinical implications in the use of these compounds.

scholarly journals Different Expression of Mitochondrial and Endoplasmic Reticulum Stress Genes in Epicardial Adipose Tissue Depends on Coronary Atherosclerosis

2021 ◽  
Vol 22 (9) ◽  
pp. 4538
Author(s):  
Helena Kratochvílová ◽  
Miloš Mráz ◽  
Barbora J. Kasperová ◽  
Daniel Hlaváček ◽  
Jakub Mahrík ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Cardiac Surgery ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Mrna Expression ◽  
Coronary Atherosclerosis ◽  
Stress Genes ◽  
Valvular Surgery

The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.

scholarly journals Expression of mRNA for Adenosine A1, A2a, A2b, and A3 Receptors in HL-60 Cells: Dependence on Cell Cycle Phases

2011 ◽  
pp. 913-920 ◽  
Author(s):  
M. HOFER ◽  
L. DUŠEK ◽  
Z. HOFEROVÁ ◽  
L. STIXOVÁ ◽  
M. POSPÍŠIL
Keyword(s):  
Cell Cycle ◽  
Mrna Expression ◽  
S Phase ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
Block Method ◽  
Physiological Mechanisms ◽  
Adenosine A1 ◽  
Adenosine A2a ◽  
Adenosine A2b

The present studies investigated changes in expression of mRNA for adenosine A1, A2a, A2b, and A3 receptors in samples of HL-60 promyelocytic cells differing in the actual presence of cells in various phases of the cell cycle induced by the double thymidine block method. Real-time PCR technique was used for obtaining data on mRNA expression. Statistical analysis of the data revealed that the mRNA expression of adenosine A1, A2a, and A3 receptors is dependent on the cell cycle phase. G0/G1 and G2/M phases were characterized by a higher mRNA expression of adenosine A1 receptors and a lower one of adenosine A2a and A3 receptors whereas the opposite was true for the S phase. Interestingly, expression of mRNA of the adenosine A2b receptors was independent on the cell cycle phase. The results indicate the plasticity of mRNA expression of adenosine receptors in the investigated promyelocytic cells and its interaction with physiological mechanisms of the cell cycle.

scholarly journals Biological Effect Evaluation of Glutathione-Responsive Cyclodextrin-Based Nanosponges: 2D and 3D Studies

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2775
Author(s):  
Monica Argenziano ◽  
Federica Foglietta ◽  
Roberto Canaparo ◽  
Rita Spagnolo ◽  
Carlo Della Pepa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Mrna Expression ◽  
Cell Cycle Arrest ◽  
Cell Cultures ◽  
Disulfide Bond ◽  
Membrane Integrity ◽  
Cycle Arrest ◽  
3D Cell Cultures ◽  
2D And 3D

This study aims to evaluate the bioeffects of glutathione-responsive β-cyclodextrin-based nanosponges (GSH-NSs) on two- (2D) and three-dimensional (3D) cell cultures. The bioeffects of two types of GSH-NS formulations, with low (GSH-NS B) and high (GSH-NS D) disulfide-bond content, were evaluated on 2D colorectal (HCT116 and HT-29) and prostatic (DU-145 and PC3) cancer cell cultures. In particular, the cellular uptake of GSH-NS was evaluated, as their effects on cell growth, mitochondrial activity, membrane integrity, cell cycle distribution, mRNA expression, and reactive oxygen species production. The effect of GSH-NSs on cell growth was also evaluated on multicellular spheroids (MCS) and a comparison of the GSH-NS cell growth inhibitory activity, in terms of inhibition concentration (IC)50 values, was performed between 2D and 3D cell cultures. A significant decrease in 2D cell growth was observed at high GSH-NS concentrations, with the formulation with a low disulfide-bond content, GSH-NS B, being more cytotoxic than the formulation with a high disulfide-bond content, GSH-NS D. The cell growth decrease induced by GSH-NS was owing to G1 cell cycle arrest. Moreover, a significant down-regulation of mRNA expression of the cyclin genes CDK1, CDK2, and CDK4 and up-regulation of mRNA expression of the cyclin inhibitor genes CDKN1A and CDKN2A were observed. On the other hand, a significant decrease in MCS growth was also observed at high GSH-NS concentrations, but not influenced by the nanosponge disulfide-bond content, with the MCS IC50 values being significantly higher than those obtained on 2D cell cultures. GSH-NSs are suitable nanocarries as they provoke limited cellular effects, as cell cycle arrest only occurred at concentrations significantly higher than those used for drug delivery.

scholarly journals Involvement of the Cell Wall Integrity Pathway of Saccharomyces cerevisiae in Protection against Cadmium and Arsenate Stresses

2020 ◽  
Vol 86 (21) ◽  
Author(s):  
Todsapol Techo ◽  
Sirada Charoenpuntaweesin ◽  
Choowong Auesukaree
Keyword(s):  
Cell Cycle ◽  
Cell Wall ◽  
Molecular Mechanisms ◽  
Cell Cycle Control ◽  
Protective Role ◽  
Cell Wall Integrity ◽  
Cycle Phase ◽  
Cell Wall Biosynthesis ◽  
Cell Wall Modification ◽  
Content Type

ABSTRACT Contamination of soil and water with heavy metals and metalloids is a serious environmental problem. Cadmium and arsenic are major environmental contaminants that pose a serious threat to human health. Although toxicities of cadmium and arsenic to living organisms have been extensively studied, the molecular mechanisms of cellular responses to cadmium and arsenic remain poorly understood. In this study, we demonstrate that the cell wall integrity (CWI) pathway is involved in coping with cell wall stresses induced by cadmium and arsenate through its role in the regulation of cell wall modification. Interestingly, the Rlm1p and SBF (Swi4p-Swi6p) complex transcription factors of the CWI pathway were shown to be specifically required for tolerance to cadmium and arsenate, respectively. Furthermore, we found the PIR2 gene, encoding cell wall O-mannosylated heat shock protein, whose expression is under the control of the CWI pathway, is important for maintaining cell wall integrity during cadmium and arsenate stresses. In addition, our results revealed that the CWI pathway is involved in modulating the expression of genes involved in cell wall biosynthesis and cell cycle control in response to cadmium and arsenate via distinct sets of transcriptional regulators. IMPORTANCE Environmental pollution by metal/metalloids such as cadmium and arsenic has become a serious problem in many countries, especially in developing countries. This study shows that in the yeast S. cerevisiae, the CWI pathway plays a protective role against cadmium and arsenate through the upregulation of genes involved in cell wall biosynthesis and cell cycle control, possibly in order to modulate cell wall reconstruction and cell cycle phase transition, respectively. These data provide insights into molecular mechanisms underlying adaptive responses to cadmium and arsenate.

Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles

Cell ◽  
1992 ◽  
Vol 70 (6) ◽  
pp. 937-948 ◽  
Author(s):  
Yuxin Yin ◽  
Michael A. Tainsky ◽  
Farideh Z. Bischoff ◽  
Louise C. Strong ◽  
Geoffrey M. Wahl
Keyword(s):  
Cell Cycle ◽  
Gene Amplification ◽  
Cell Cycle Control ◽  
Mutant P53 ◽  
Wild Type ◽  
Wild Type P53 ◽  
In Cells
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