Apoptosis or senescence-like growth arrest: influence of cell-cycle position, p53, p21 and bax in H2O2 response of normal human fibroblasts

2000 ◽  
Vol 347 (2) ◽  
pp. 543-551 ◽  
Author(s):  
Qin M. CHEN ◽  
Juping LIU ◽  
Jessica B. MERRETT
Keyword(s):  
Cell Cycle ◽  
Caspase 3 ◽  
Human Fibroblasts ◽  
Growth Arrest ◽  
S Phase ◽  
Phase Cell ◽  
G1 Arrest ◽  
Apoptotic Cells ◽  
Early Passage ◽  
Bax Protein

Early-passage human diploid fibroblasts (HDFs) undergo senescence-like growth arrest in response to sublethal concentrations of H2O2 [Chen and Ames (1994) Proc. Natl. Acad. Sci. U.S.A. 95, 4130-4134]. We determine here whether H2O2 can cause apoptosis in HDFs and the molecular changes that differ between apoptosis and senescence-like growth arrest. When exponentially growing early-passage IMR-90 cells were treated for 2 h with 50-200 μM (or 0.25-1 pmol/cell) H2O2, a fraction of cells detached at 16-32 h after the treatment. The cells remaining attached were growth-arrested and developed features of senescence in 1 week. The detached cells showed caspase-3 activation and typical morphological changes associated with apoptosis. Caspase-3 activation was H2O2 dose-dependent and preceded nuclear condensation or plasma membrane leakage. Apoptotic cells were mainly distributed in the S-phase of the cell cycle, while growth-arrested cells exhibited predominantly G1- and G2/M-phase distributions. H2O2 pretreatment induced G1 arrest and prohibited induction of apoptosis by a subsequent H2O2 challenge. The p53 protein showed an average 6.1-fold elevation in apoptotic cells and a 3.5-fold elevation in growth-arrested cells. Reduction of p53 levels with human papillomavirus E6 protein prohibited the activation of caspase-3 and decreased the proportion of apoptotic cells. Growth-arrested cells had elevated p21, while p21 was absent in apoptotic cells. Bcl-2 was elevated in both growth-arrested and apoptotic cells. Finally, although the overall level of bax did not change in growth-arrested or apoptotic cells, the solubility of bax protein increased in apoptotic cells. Our data suggest that in contrast with growth-arrested cells, apoptotic cells show an S-phase cell cycle distribution, a higher degree of p53 elevation, an absence of p21 protein and increased solubility of bax protein.

Involvement of the p38 MAPK signaling pathway in S-phase cell-cycle arrest induced by Furazolidone in human hepatoma G2 cells

2012 ◽  
Vol 33 (12) ◽  
pp. 1500-1505 ◽  
Author(s):  
Yu Sun ◽  
Shusheng Tang ◽  
Xi Jin ◽  
Chaoming Zhang ◽  
Wenxia Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
S Phase ◽  
Mapk Signaling Pathway ◽  
Phase Cell ◽  
Human Hepatoma ◽  
Cycle Arrest

scholarly journals S-Phase Cell Cycle Arrest, Apoptosis, and Molecular Mechanisms of Aplasia Ras homolog Member I–Induced Human Ovarian Cancer SKOV3 Cell Lines

2014 ◽  
Vol 24 (4) ◽  
pp. 629-634 ◽  
Author(s):  
Qiaoying Zhu ◽  
Jianming Hu ◽  
Huijuan Meng ◽  
Yufei Shen ◽  
Jinhua Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Significant Inhibition ◽  
S Phase ◽  
Phase Cell ◽  
Cell Cycle Distribution ◽  
Human Ovarian Cancer ◽  
Skov3 Cell ◽  
Skov3 Cells

ObjectiveAplasia Ras homolog member I (ARHI) is associated with human ovarian cancer (HOC) growth and proliferation; however, the mechanisms are unclear. The purpose of this study was to investigateARHIeffects in HOC SKOV3 cells.MethodsWe transfected SKOV3 cells with PIRES2-EGFP-ARHI and measured growth inhibition rates, cell cycle distribution, apoptosis rates, and expression of P-STAT3 (phosphorylated signal transduction and activators of transcription 3) and P-ERK (phosphorylated extracellular signal regulated protein kinase).ResultsOur data showed significant inhibition of growth, significantly increased S-phase arrest and apoptosis rates, and reduction of P-STAT3 and P-ERK1/2 expression levels.ConclusionsWe propose the mechanism may involveARHI-induced phosphorylation of ERK1/2 and STAT3 protein kinases, thereby blocking proliferation signaling pathways, to induce HOC SKOV3 apoptosis.

scholarly journals Cdc5L interacts with ATR and is required for the S‐phase cell‐cycle checkpoint

EMBO Reports ◽  
2009 ◽  
Vol 10 (9) ◽  
pp. 1029-1035 ◽  
Author(s):  
Nianxiang Zhang ◽  
Ramandeep Kaur ◽  
Shamima Akhter ◽  
Randy J Legerski
Keyword(s):  
Cell Cycle ◽  
S Phase ◽  
Cell Cycle Checkpoint ◽  
Phase Cell ◽  
Cycle Checkpoint

scholarly journals Xanthohumol Induces Growth Inhibition and Apoptosis in Ca Ski Human Cervical Cancer Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Wai Kuan Yong ◽  
Sri Nurestri Abd Malek
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Morphological Changes ◽  
S Phase ◽  
Phase Cell ◽  
Cervical Cancer Cell Line ◽  
Dependent Manner ◽  
Cervical Cancer Cells

We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. Xanthohumol is a prenylated chalcone naturally found in hop plants, previously reported to be an effective anticancer agent in various cancer cell lines. The present study showed that xanthohumol was effective to inhibit proliferation of Ca Ski cells based on IC50values using sulforhodamine B (SRB) assay. Furthermore, cellular and nuclear morphological changes were observed in the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. In addition, 48-hour long treatment with xanthohumol triggered externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells. Additionally, xanthohumol mediated S phase arrest in cell cycle analysis and increased activities of caspase-3, caspase-8, and caspase-9. On the other hand, Western blot analysis showed that the expression levels of cleaved PARP, p53, and AIF increased, while Bcl-2 and XIAP decreased in a dose-dependent manner. Taken together, these findings indicate that xanthohumol-induced cell death might involve intrinsic and extrinsic apoptotic pathways, as well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. This work suggests that xanthohumol is a potent chemotherapeutic candidate for cervical cancer.

Cloning of a human S-phase cell cycle gene: use of transient expression for screening

1987 ◽  
Vol 7 (2) ◽  
pp. 775-779
Author(s):  
A Fainsod ◽  
G Diamond ◽  
M Marcus ◽  
F H Ruddle
Keyword(s):  
Cell Cycle ◽  
Genomic Library ◽  
Chinese Hamster ◽  
Chinese Hamster Cell ◽  
S Phase ◽  
Phase Cell ◽  
Cell Cycle Gene ◽  
Temperature Sensitive ◽  
Specific Cell ◽  
Restrictive Temperature

We report here the cloning of a human cell cycle gene capable of complementing a temperature-sensitive (ts) S-phase cell cycle mutation in a Chinese hamster cell line. Cloning was performed as follows. A human genomic library in phage lambda containing 600,000 phages was screened with labeled cDNA synthesized from an mRNA fraction enriched for the specific cell cycle gene message. Plaques containing DNA inserts which hybridized to the cDNA were picked, and their DNAs were assayed for transient complementation in DNA transformation experiments. The transient complementation assay we developed is suitable for most cell cycle genes and indeed for many genes whose products are required for cell proliferation. Of 845 phages screened, 1 contained an insert active in transient complementation of the ts cell cycle mutation. Introduction of this phage into the ts cell cycle mutant also gave rise to stable transformants which grew normally at the restrictive temperature for the ts mutant cells.

Ciprofloxacin-mediated induction of S-phase cell cycle arrest and apoptosis in COLO829 melanoma cells

2018 ◽  
Vol 70 (1) ◽  
pp. 6-13 ◽  
Author(s):  
Artur Beberok ◽  
Dorota Wrześniok ◽  
Aldona Minecka ◽  
Jakub Rok ◽  
Marcin Delijewski ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Melanoma Cells ◽  
S Phase ◽  
Phase Cell ◽  
Cycle Arrest
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