A β-carboline derivative-based nickel(ii) complex as a potential antitumor agent: synthesis, characterization, and cytotoxicity

A novel nickel(ii) complex was synthesized and characterized. It significantly induced cell cycle arrest at S phase, and caused the down-regulation of p-AKT, cyclin E, cyclin A and CDK2 and the up-regulation of p27.

Download Full-text

HCV NS2 protein inhibits cell proliferation and induces cell cycle arrest in the S-phase in mammalian cells through down-regulation of cyclin A expression

Virus Research ◽

10.1016/j.virusres.2006.02.004 ◽

2006 ◽

Vol 121 (2) ◽

pp. 134-143 ◽

Cited By ~ 32

Author(s):

Xiao-Jun Yang ◽

Jing Liu ◽

Li Ye ◽

Qing-Jiao Liao ◽

Jian-Guo Wu ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cell Cycle Arrest ◽

Mammalian Cells ◽

Cyclin A ◽

S Phase ◽

Down Regulation ◽

Cycle Arrest

Download Full-text

The Cyclin E/Cdk2 Substrate p220NPAT Is Required for S-Phase Entry, Histone Gene Expression, and Cajal Body Maintenance in Human Somatic Cells

Molecular and Cellular Biology ◽

10.1128/mcb.23.23.8586-8600.2003 ◽

2003 ◽

Vol 23 (23) ◽

pp. 8586-8600 ◽

Cited By ~ 76

Author(s):

Xin Ye ◽

Yue Wei ◽

Grzegorz Nalepa ◽

J. Wade Harper

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cyclin E ◽

S Phase ◽

Cajal Body ◽

Histone H4 ◽

Cycle Arrest ◽

Histone Transcription ◽

Phase Entry ◽

Hct116 Cells

ABSTRACT Cyclin E/Cdk2, a central regulator of the G1/S transition, coordinates multiple cell cycle events, including DNA replication, centrosome duplication, and activation of the E2F transcriptional program. Recent studies suggest a role for cyclin E/Cdk2 in activation of histone transcription during S phase via the Cajal body-associated protein p220NPAT, and in addition, p220 can promote S-phase entry independently of histone transcriptional activation when overexpressed. Here we have examined the requirement for p220 in histone transcription, cell cycle progression, and Cajal body function through analysis of human somatic HCT116 cells engineered to contain a conditional p220 allele. p220 is required for proliferation of HCT116 cells, as assessed after expression of Cre recombinase in p220flox/− cells. This defect was due to an inability of these cells to transit from G0/G1 into S phase, and cell cycle arrest occurred in the presence of elevated Cdk2 kinase activity. Expression of human papillomavirus E7, but not E6, eliminated cell cycle arrest in response to p220 depletion. Optimal expression of all four core histone genes required p220, as did optimal transcription of a histone H4 promoter-luciferase construct. Basal histone H4 expression in G0/G1, although p220 dependent, occurs in the absence of detectable phosphorylation of p220 on Cdk2 sites. Cells lacking p220 displayed defects in the localization of the Cajal body component p80coilin as cells progressed from G0 to S phase in response to mitogenic signals. These finding indicate that p220 is an essential downstream component of the cyclin E/Cdk2 signaling pathway and functions to coordinate multiple elements of the G1/S transition.

Download Full-text

Retinoic acid–induced cell cycle arrest of human myeloid cell lines is associated with sequential down-regulation of c-Myc and cyclin E and posttranscriptional up-regulation of p27Kip1

Blood ◽

10.1182/blood.v99.6.2199 ◽

2002 ◽

Vol 99 (6) ◽

pp. 2199-2206 ◽

Cited By ~ 103

Author(s):

Anna Dimberg ◽

Fuad Bahram ◽

Inger Karlberg ◽

Lars-Gunnar Larsson ◽

Kenneth Nilsson ◽

...

Keyword(s):

Cell Cycle ◽

Retinoic Acid ◽

Cell Cycle Arrest ◽

Molecular Mechanisms ◽

Cyclin E ◽

Myeloid Cells ◽

Myeloid Cell ◽

G1 Arrest ◽

Down Regulation ◽

Cycle Arrest

Abstract All-trans retinoic acid (ATRA) is a potential therapeutic agent for the treatment of hematopoietic malignancies, because of its function as an inducer of terminal differentiation of leukemic blasts. Although the efficacy of ATRA as an anticancer drug has been demonstrated by the successful treatment of acute promyelocytic leukemia (APL), the molecular mechanisms of ATRA-induced cell cycle arrest of myeloid cells have not been fully investigated. In this study, we show that the onset of ATRA-induced G0/G1 arrest of human monoblastic U-937 cells is linked to a sharp down-regulation of c-Myc and cyclin E levels and an increase in p21WAF1/CIP1 expression. This is followed by an increase in p27Kip1 protein expression due to enhanced protein stability. The importance of an early decrease in Myc expression for these events was demonstrated by the failure of a U-937 subline with constitutive exogenous expression of v-Myc to cell cycle arrest and regulate cyclin E and p27Kip1 in response to ATRA. Preceding the initiation of G1 arrest, a transient rise in retinoblastoma protein (pRb), p107, and cyclin A levels was detected. Later, a rapid fall in the levels of cyclins A and B and a coordinate dephosphorylation of pRb at Ser780, Ser795, and Ser807/811 coincided with the accumulation of cells in G1. These results thus identify a decrease in c-Myc and cyclin E levels and a posttranscriptional up-regulation of p27Kip1 as important early changes, and position them in the complex chain of events regulating ATRA-induced cell cycle arrest of myeloid cells.

Download Full-text

Induction of cell cycle arrest via the p21, p27–cyclin E,A/Cdk2 pathway in SMMC-7721 hepatoma cells by clioquinol

Acta Pharmaceutica ◽

10.1515/acph-2015-0034 ◽

2015 ◽

Vol 65 (4) ◽

pp. 463-471 ◽

Cited By ~ 11

Author(s):

Zhiwei Huang ◽

Lianqiu Wang ◽

Lifeng Chen ◽

Yifei Zhang ◽

Ping Shi

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Cycle Progression ◽

Therapeutic Potential ◽

Cyclin E ◽

S Phase ◽

Dependent Manner ◽

Hepatic Cells ◽

Cycle Arrest ◽

First Time

Abstract Clioquinol has been shown to have anticancer activity in several carcinoma cells. In this study, we preliminarily examined the effect of clioquinol in human SMMC-7721 hepatoma and QSG-7701 normal hepatic cells. Our results indicated that clioquinol did not significantly affect survival of QSG-7701 cells, whereas it reduced cell viability in a concentration- and time-dependent manner in SMMC-7721 cells. Clioquinol did not trigger autophagy and apoptosis, while it induced cell cycle arrest in the S-phase in SMMC- 7721 cells. Additionally, down-regulation of cyclin D1, A2, E1, Cdk2 and up-regulation of p21, p27 were detected after the treatment with clioquinol. The results demonstrated for the first time that clioquinol suppressed cell cycle progression in the S-phase in SMMC-7721 cells via the p21, p27-cyclin E,A/Cdk2 pathway. This suggests that clioquinol may have a therapeutic potential as an anticancer drug for certain malignances.

Download Full-text

Nucleolin Down-Regulation Is Involved in ADP-Induced Cell Cycle Arrest in S Phase and Cell Apoptosis in Vascular Endothelial Cells

PLoS ONE ◽

10.1371/journal.pone.0110101 ◽

2014 ◽

Vol 9 (10) ◽

pp. e110101 ◽

Cited By ~ 5

Author(s):

Wenmeng Wang ◽

Junqing Luo ◽

Fang Xiang ◽

Xueting Liu ◽

Manli Jiang ◽

...

Keyword(s):

Cell Cycle ◽

Endothelial Cells ◽

Cell Cycle Arrest ◽

Cell Apoptosis ◽

Vascular Endothelial Cells ◽

S Phase ◽

Vascular Endothelial ◽

Down Regulation ◽

Cycle Arrest

Download Full-text

Theabrownin Induces Cell Apoptosis and Cell Cycle Arrest of Oligodendroglioma and Astrocytoma in Different Pathways

Frontiers in Pharmacology ◽

10.3389/fphar.2021.664003 ◽

2021 ◽

Vol 12 ◽

Author(s):

J. Y. Fu ◽

C. X. Jiang ◽

M. Y. Wu ◽

R. Y. Mei ◽

A. F. Yang ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Antitumor Agent ◽

Dependent Manner ◽

Tb Treatment ◽

Cycle Arrest ◽

Candidate Drug ◽

Dose Dependent ◽

U251 Cells ◽

Potential Antitumor

Theabrownin (TB), a natural compound present in the fresh leaves of green tea, is a potential antitumor agent. However, so far whether and how TB affects glioma is unclear. In this study, we investigated the effect of TB on astroglioma and oligodendroglioma cells. Surprisingly, TB significantly reduced the viabilities of HOG and U251 cells in a dose-dependent manner, which was accompanied by the upregulation of active-Casp-3, Bax, and PTEN; meanwhile, the antiapoptotic gene Bcl-2 was downregulated. In addition, TB treatment induced cell cycle arrest at the G1 and G2/M phases in HOG and U251 cells, respectively. TB treatment caused the downregulating of c-myc, cyclin D, CDK2, and CDK4 and upregulating of p21 and p27 in the HOG cell, while TB increased P53, p21, and p27 levels and decreased the levels of cell cycle regulator proteins such as CDK and cyclin A/B in the U251 cells. Therefore, the c-myc- and P53-related mechanisms were proposed for cell cycle arrest in these two glioma cell lines, respectively. Overall, our findings indicated that TB could be a novel candidate drug for the treatment of gliomas.

Download Full-text

Phenylpropanoid-based sulfonamide promotes cyclin D1 and cyclin E down-regulation and induces cell cycle arrest at G1/S transition in estrogen positive MCF-7 cell line

Toxicology in Vitro ◽

10.1016/j.tiv.2019.04.023 ◽

2019 ◽

Vol 59 ◽

pp. 150-160 ◽

Cited By ~ 6

Author(s):

Helloana Azevedo-Barbosa ◽

Guilherme Álvaro Ferreira-Silva ◽

Carolina Faria Silva ◽

Thiago Belarmino de Souza ◽

Danielle Ferreira Dias ◽

...

Keyword(s):

Cell Cycle ◽

Cyclin D1 ◽

Cell Cycle Arrest ◽

Cell Line ◽

Cyclin E ◽

Down Regulation ◽

Cycle Arrest ◽

Mcf 7

Download Full-text

Cytotoxic and Anti-proliferative Effects of Moringa oleifera Lam. on HeLa Cells

The Natural Products Journal ◽

10.2174/2210315511666210826165242 ◽

2021 ◽

Vol 11 ◽

Author(s):

Krishnambal Govender ◽

Indres Moodley ◽

Raveen Parboosing

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Hela Cells ◽

Caspase 3 ◽

Cyclin E ◽

Cyclin B1 ◽

M Cell ◽

Down Regulation ◽

Cycle Arrest ◽

Dose Dependent

Background: The aim of the study was to determine the mechanism of Moringa oleifera-induced apoptosis in HeLa cells. HeLa cells over-express cyclin E and cyclin B1, abrogate G0-G1 and G2-M cell cycle arrest, promoting tumorigenesis. Cyclin E, cyclin B1, E2F1 and telomerase expression, and caspase-3 and -7 activation were assessed after 24-treatment with M. oleifera leaf fractions. Material and methods: Apoptosis through caspase-3 and caspase-7 activation was determined quantitatively by the FAM FLICA™ Caspase-3/7 assay. Cyclin E, cyclin B1 and E2F1 were quantified by flow cytometry. Telomerase was evaluated by Telomeric repeat amplification protocol (TRAP reaction). The effects on colony formation were assessed by seeding treated cells in six-well plates for 7 days under culture conditions. The MTT assay was used to determine cell survival. Results: HeLa cells treated for 24 hours with M. oleifera leaf fractions showed dose-dependent cytotoxicity, activation of caspases-3 and -7; down-regulation of cyclin E, cyclin B1, E2F1, and inhibition of telomerase expression. Cell cycle analysis of the dead cell population showed G2-M cell-cycle arrest. Conclusion: M. oleifera leaf fractions triggered apoptosis through the mitochondrial pathway and cell cycle arrest at G2-M phase in HeLa cells after 24-hour treatment, through down-regulation of cyclin E and cyclin B1 expression; and caspase-3 and -7 activation. In addition, M. oleifera leaf extract induces senescence in HeLa cells through the down-regulation of telomerase. Colony formation and cell proliferation were inhibited in a dose-dependent manner, corresponding with telomerase inhibition.

Download Full-text