Curcumin induces G2/M cell cycle arrest in a p53-dependent manner and upregulates ING4 expression in human glioma

Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

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Cathepsin L suppression increases the radiosensitivity of human glioma U251 cells via G2/M cell cycle arrest and DNA damage

Acta Pharmacologica Sinica ◽

10.1038/aps.2015.36 ◽

2015 ◽

Vol 36 (9) ◽

pp. 1113-1125 ◽

Cited By ~ 16

Author(s):

Qing-qing Zhang ◽

Wen-juan Wang ◽

Jun Li ◽

Neng Yang ◽

Gang Chen ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Cycle Arrest ◽

Cathepsin L ◽

Human Glioma ◽

M Cell ◽

Cycle Arrest ◽

U251 Cells

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Cucurbitacin B Induced ATM-Mediated DNA Damage Causes G2/M Cell Cycle Arrest in a ROS-Dependent Manner

PLoS ONE ◽

10.1371/journal.pone.0088140 ◽

2014 ◽

Vol 9 (2) ◽

pp. e88140 ◽

Cited By ~ 42

Author(s):

Jiajie Guo ◽

Guosheng Wu ◽

Jiaolin Bao ◽

Wenhui Hao ◽

Jinjian Lu ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Cycle Arrest ◽

Dependent Manner ◽

M Cell ◽

Cucurbitacin B ◽

Cycle Arrest

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HIV-1 Vpr induces cell cycle arrest and enhances viral gene expression by depleting CCDC137

eLife ◽

10.7554/elife.55806 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Fengwen Zhang ◽

Paul D Bieniasz

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Biological Effects ◽

Viral Gene Expression ◽

Viral Gene ◽

Dependent Manner ◽

M Cell ◽

Cycle Arrest ◽

Hiv 1

The HIV-1 Vpr accessory protein induces ubiquitin/proteasome-dependent degradation of many cellular proteins by recruiting them to a cullin4A-DDB1-DCAF1 complex. In so doing, Vpr enhances HIV-1 gene expression and induces (G2/M) cell cycle arrest. However, the identities of Vpr target proteins through which these biological effects are exerted are unknown. We show that a chromosome periphery protein, CCDC137/cPERP-B, is targeted for depletion by HIV-1 Vpr, in a cullin4A-DDB1-DCAF1 dependent manner. CCDC137 depletion caused G2/M cellcycle arrest, while Vpr-resistant CCDC137 mutants conferred resistance to Vpr-induced G2/M arrest. CCDC137 depletion also recapitulated the ability of Vpr to enhance HIV-1 gene expression, particularly in macrophages. Our findings indicate that Vpr promotes cell-cycle arrest and HIV-1 gene expression through depletion of CCDC137.

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Harmine Hydrochloride Mediates the Induction of G2/M Cell Cycle Arrest in Breast Cancer Cells by Regulating the MAPKs and AKT/FOXO3a Signaling Pathways

Molecules ◽

10.3390/molecules26216714 ◽

2021 ◽

Vol 26 (21) ◽

pp. 6714

Author(s):

Chae Won Ock ◽

Gi Dae Kim

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Signaling Pathways ◽

Cyclin B1 ◽

New Drugs ◽

Dependent Manner ◽

M Cell ◽

Cycle Arrest ◽

Mcf 7

Breast cancer (BC) is one of the most common causes of death among women worldwide. Recently, interest in novel approaches for BC has increased by developing new drugs derived from natural products with reduced side effects. This study aimed to treat BC cells with harmine hydrochloride (HMH) to identify its anticancer effects and mechanisms. HMH treatment suppressed cell growth, migration, invasion, and colony formation in MCF-7 and MDA-MB-231 cells, regardless of the hormone signaling. It also reduced the phosphorylation of PI3K, AKT, and mTOR and increased FOXO3a expression. Additionally, HMH treatment increased p38 phosphorylation in MCF-7 cells and activated c-Jun N-terminal kinase (JNK) phosphorylation in MDA-MB-231 cells in a dose-dependent manner, where activated p38 and JNK increased FOXO3a expression. Activated FOXO3a increased the expression of p53, p21, and their downstream proteins, including p-cdc25, p-cdc2, and cyclin B1, to induce G2/M cell cycle arrest. Furthermore, HMH inhibited the PI3K/AKT/mTOR pathway by significantly reducing p-AKT expression in combination with LY294002, an AKT inhibitor. These results indicate that mitogen-activated protein kinases (MAPKs) and AKT/FOXO3a signaling pathways mediate the induction of cell cycle arrest following HMH treatment. Therefore, HMH could be a potential active compound for anticancer bioactivity in BC cells.

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HIV-1 Vpr induces cell cycle arrest and enhances viral gene expression by depleting CCDC137

10.1101/2019.12.24.888230 ◽

2019 ◽

Cited By ~ 1

Author(s):

Fengwen Zhang ◽

Paul D. Bieniasz

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Biological Effects ◽

Viral Gene Expression ◽

Viral Gene ◽

Dependent Manner ◽

M Cell ◽

Cycle Arrest ◽

Hiv 1

SummaryThe HIV-1 Vpr accessory protein induces ubiquitin/proteasome-dependent degradation of many cellular proteins by recruiting them to a cullin4A-DDB1-DCAF1 complex. In so doing, Vpr enhances HIV-1 gene expression and induces (G2/M) cell cycle arrest. However, the identities of Vpr target proteins through which these biological effects are exerted are unknown. We show that a chromosome periphery protein, CCDC137/cPERP-B, is targeted for depletion by HIV-1 Vpr, in a cullin4A-DDB1-DCAF1 dependent manner. CCDC137 depletion caused G2/M cell-cycle arrest, while Vpr-resistant CCDC137 mutants conferred resistance to Vpr-induced G2/M arrest. CCDC137 depletion also recapitulated the ability of Vpr to enhance HIV-1 gene expression, particularly in macrophages. Our findings indicate that Vpr promotes cell-cycle arrest and HIV-1 gene expression through depletion of CCDC137.

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The Polyphenols α-Mangostin and Nordihydroguaiaretic Acid Induce Oxidative Stress, Cell Cycle Arrest, and Apoptosis in a Cellular Model of Medulloblastoma

Molecules ◽

10.3390/molecules26237230 ◽

2021 ◽

Vol 26 (23) ◽

pp. 7230

Author(s):

Alberto Rojas-Ochoa ◽

Emilio J. Córdova ◽

Adela Carrillo-García ◽

Marcela Lizano ◽

José Pedraza-Chaverri ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Cell Death ◽

Cell Cycle Arrest ◽

Cell Line ◽

Nordihydroguaiaretic Acid ◽

Antitumoral Activity ◽

Dependent Manner ◽

M Cell ◽

Cycle Arrest

Medulloblastoma is a common malignant brain tumor in the pediatric age. The current therapeutics present serious collateral effects. Polyphenols α-mangostin and nordihydroguaiaretic acid (NDGA) exert potent antitumoral activity in different cancer models, although their antitumoral effects have not been described in medulloblastoma cells yet. This study aimed to examine the proapoptotic effects of these polyphenols on human medulloblastoma cells. Medulloblastoma cell line Daoy was incubated with increasing concentrations of α-mangostin or NDGA for 24 h. The cell viability was analyzed using crystal violet and trypan blue dyes. Determination of the glutathione (GSH)/glutathione disulfide (GSSG) ratio and levels of carbonylated proteins was performed to evaluate the oxidative stress. Cell cycle progression and induction of cell death by fluorochrome-couple and TUNEL assays were evaluated using flow cytometry assays. Individual treatments with α-mangostin or NDGA decreased the viability of Daoy cells in a dose-dependent manner, inducing G2/M and S-G2/M cell cycle arrest, respectively. Both polyphenols induced cell death and increased oxidative stress. Very interestingly, α-mangostin showed more potent effects than NDGA. Our results indicate that α-mangostin and NDGA exert important cytostatic and cytotoxic effects in the Daoy cell line. These data highlight the potential usefulness of these compounds as an alternative strategy in medulloblastoma treatment.

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