Faculty Opinions recommendation of Coordination of mitochondrial bioenergetics with G1 phase cell cycle progression.

2008 ◽  
Author(s):  
Robert Abraham
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Phase Cell ◽  
G1 Phase ◽  
Mitochondrial Bioenergetics ◽  
Cycle Progression

scholarly journals Involvement of Rho proteins in G1 phase cell cycle progression

2013 ◽  
Vol 67 ◽  
pp. 15-25 ◽  
Author(s):  
Anna Klimaszewska-Wiśniewska ◽  
Jakub Marcin Nowak ◽  
Agnieszka Żuryń ◽  
Alina Grzanka
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Phase Cell ◽  
G1 Phase ◽  
Rho Proteins ◽  
Cycle Progression

Rapamycin, Inhibitor of Mtor Kinase, Sensitizes Leukemia Cells to Fludarabine-Induced Apoptosis, but Protects Survival of Normal Lymphocytes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4497-4497 ◽  
Author(s):  
Piotr Smolewski ◽  
Barbara Cebula ◽  
Dorota Wierzbicka ◽  
Anna Linke ◽  
Krzysztof Jamroziak ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mtt Assay ◽  
Cell Cycle Progression ◽  
Cyclin A ◽  
Leukemia Cells ◽  
Phase Cell ◽  
G1 Phase ◽  
Cycle Progression ◽  
Mtor Kinase ◽  
Induced Apoptosis

Abstract Background: The mTOR kinase inhibitor, rapamycin (RAPA), inhibits cell growth by G1 phase cell cycle arrest. RAPA-induced cytotoxicity against acute lymphoblastic leukemia (ALL) cells was recently reported. Aim: We investigated cytotoxicity of RAPA alone or in combination with fludarabine (FA), a cytostatic active in G1 phase, in ALL cells as well as in healthy lymphocytes. Methods: NALM-6 cells (pre-B ALL-derived cell line), and phytohemaglutynin (PHA)-stimulated normal lymphocytes were treated for 24–48h with different concentrations of RAPA (0,05–500ng/ml), alone or in combination with 0.1–50.0mM FA. Some samples were initially incubated with RAPA for 24h and then FA was added for the next 24h. Untreated cultures and treated with RAPA, FA or PHA alone served as respective controls. The pro-apoptotic effect was assessed by both Annexin-V and TUNEL assays and presented as an apoptotic index (AI). Cell cycle was analyzed by DNA content distribution in propydium iodide/RN-ase stained cells. Additionally, intracellular expression of cyclin A, D3 and E was evaluated. All fluorescence measurements were performed by flow cytometry. Overall cytotoxicity was evaluated by MTT assay. Results: RAPA was found to exert dual effect on NALM-6 cells. In lower concentrations (0.05–5ng/ml) RAPA exclusively inhibited proliferation, arresting NALM-6 cells in G1 phase of cell cycle. An increasing evidence of apoptosis, along to enhancing cytotoxicity in MTT assay was observed higher RAPA doses (10–500ng/ml). When NALM-6 were treated with RAPA+FA, the highest AIs were found for the combination of 0.5 or 1.0ng/ml RAPA with 1nM FA. Median AI induced at 24h by 1.0ng/ml RAPA+FA was 12.4%, comparing to with RAPA or FA alone (AIs 1.9% and 4.8%, respectively; both p<0.0001). This effect was synergistic, with the combination index (CI) 0.68. Treatment with RAPA+FA significantly downregulated cyclin A and E expression, comparing to both untreated control and cultures treated with single agents. Importantly, 24h pretreatment of NALM-6 cells with RAPA additionally accelerated apoptosis. In PHA-stimulated lymphocytes, cytotoxicity induced by corresponding concentrations of drugs was moderately lower, than in NALM-6. In contrast to leukemic cells, 24h pretreatment of normal lymphocytes with RAPA resulted in distinct prevention of FA-induced cytotoxicity. It was accompanied by the block in PHA-induced cell cycle progression to phase S. Moreover, this blocking effect of RAPA was reversible, when after 24h of treatment lymphocytes were rinsed and placed back in fresh RAPA-free medium for the next 24h of culture. Conclusions: In low concentration RAPA sensitizes NALM-6 cells to FA-induced apoptosis. Pretreatment with RAPA enhances cytotoxic effect on leukemia cells, but not on normal lymphocytes. RAPA administrated prior to FA blocks reversible cell cycle progression, preventing lymphocyte from FA cytotoxicity. These data provide rationale for future applying RAPA in the combination with purine nucleoside analogues for treatment of lymphoproliferative diseases. Moreover, they suggest, that the choice of optimal doses of both RAPA and the cytostatic may result in selective anti-tumor treatment, with protection of normal cells.

scholarly journals PAI-1 Leads to G1-Phase Cell-Cycle Progression through Cyclin D3/cdk4/6 Upregulation

2014 ◽  
Vol 12 (3) ◽  
pp. 322-334 ◽  
Author(s):  
Evan Gomes Giacoia ◽  
Makito Miyake ◽  
Adrienne Lawton ◽  
Steve Goodison ◽  
Charles J. Rosser
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cyclin D3 ◽  
Phase Cell ◽  
G1 Phase ◽  
Cycle Progression ◽  
Pai 1

scholarly journals Influenza A Virus Replication Induces Cell Cycle Arrest in G0/G1 Phase

2010 ◽  
Vol 84 (24) ◽  
pp. 12832-12840 ◽  
Author(s):  
Yuan He ◽  
Ke Xu ◽  
Bjoern Keiner ◽  
Jianfang Zhou ◽  
Volker Czudai ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Influenza A Virus ◽  
Influenza A ◽  
Cell Cycle Progression ◽  
Virus Production ◽  
Phase Cell ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Infected Cells

ABSTRACT Many viruses interact with the host cell division cycle to favor their own growth. In this study, we examined the ability of influenza A virus to manipulate cell cycle progression. Our results show that influenza A virus A/WSN/33 (H1N1) replication results in G0/G1-phase accumulation of infected cells and that this accumulation is caused by the prevention of cell cycle entry from G0/G1 phase into S phase. Consistent with the G0/G1-phase accumulation, the amount of hyperphosphorylated retinoblastoma protein, a necessary active form for cell cycle progression through late G1 into S phase, decreased after infection with A/WSN/33 (H1N1) virus. In addition, other key molecules in the regulation of the cell cycle, such as p21, cyclin E, and cyclin D1, were also changed and showed a pattern of G0/G1-phase cell cycle arrest. It is interesting that increased viral protein expression and progeny virus production in cells synchronized in the G0/G1 phase were observed compared to those in either unsynchronized cells or cells synchronized in the G2/M phase. G0/G1-phase cell cycle arrest is likely a common strategy, since the effect was also observed in other strains, such as H3N2, H9N2, PR8 H1N1, and pandemic swine H1N1 viruses. These findings, in all, suggest that influenza A virus may provide favorable conditions for viral protein accumulation and virus production by inducing a G0/G1-phase cell cycle arrest in infected cells.

scholarly journals Regulation of Cell Cycle Progression by Growth Factor-Induced Cell Signaling

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3327
Author(s):  
Zhixiang Wang
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Tyrosine Kinases ◽  
Cell Cycle Progression ◽  
Phase Cell ◽  
Growth Factor Signaling ◽  
Cycle Progression ◽  
M Phase

The cell cycle is the series of events that take place in a cell, which drives it to divide and produce two new daughter cells. The typical cell cycle in eukaryotes is composed of the following phases: G1, S, G2, and M phase. Cell cycle progression is mediated by cyclin-dependent kinases (Cdks) and their regulatory cyclin subunits. However, the driving force of cell cycle progression is growth factor-initiated signaling pathways that control the activity of various Cdk–cyclin complexes. While the mechanism underlying the role of growth factor signaling in G1 phase of cell cycle progression has been largely revealed due to early extensive research, little is known regarding the function and mechanism of growth factor signaling in regulating other phases of the cell cycle, including S, G2, and M phase. In this review, we briefly discuss the process of cell cycle progression through various phases, and we focus on the role of signaling pathways activated by growth factors and their receptor (mostly receptor tyrosine kinases) in regulating cell cycle progression through various phases.

scholarly journals (S)-10-Hydroxycamptothecin Inhibits Esophageal Squamous Cell Carcinoma Growth In Vitro and In Vivo Via Decreasing Topoisomerase I Enzyme Activity

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1964 ◽  
Author(s):  
Mengqiu Song ◽  
Shuying Yin ◽  
Ran Zhao ◽  
Kangdong Liu ◽  
Joydeb Kumar Kundu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Enzymatic Activity ◽  
Topoisomerase I ◽  
Cell Cycle Progression ◽  
Caspase 3 ◽  
Cyclin B1 ◽  
Phase Cell ◽  
Cycle Progression

Topoisomerase (TOP) I plays a major role in the process of supercoiled DNA relaxation, thereby facilitating DNA replication and cell cycle progression. The expression and enzymatic activity of TOP I is positively correlated with tumor progression. Although the anticancer activity of (S)-10-Hydroxycamptothecin (HCPT), a TOP I specific inhibitor, has been reported in various cancers, the effect of HCPT on esophageal cancer is yet to be examined. In this study, we investigate the potential of HCPT to inhibit the growth of ESCC cells in vitro and verify its anti-tumor activity in vivo by using a patient-derived xenograft (PDX) tumor model in mice. Our study revealed the overexpression of TOP I in ESCC cells and treatment with HCPT inhibited TOP I enzymatic activity at 24 h and decreased expression at 48 h and 72 h. HCPT also induced DNA damage by increasing the expression of H2A.XS139. HCPT significantly decreased the proliferation and anchorage-independent growth of ESCC cells (KYSE410, KYSE510, KYSE30, and KYSE450). Mechanistically, HCPT inhibited the G2/M phase cell cycle transition, decreased the expression of cyclin B1, and elevated p21 expression. In addition, HCPT stimulated ESCC cells apoptosis, which was associated with elevated expression of cleaved PARP, cleaved caspase-3, cleaved caspase-7, Bax, Bim, and inhibition of Bcl-2 expression. HCPT dramatically suppressed PDX tumor growth and decreased the expression of Ki-67 and TOP I and increased the level of cleaved caspase-3 and H2A.XS139 expression. Taken together, our data suggested that HCPT inhibited ESCC growth, arrested cell cycle progression, and induced apoptosis both in vitro and in vivo via decreasing the expression and activity of TOP I enzyme.

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