Induction of G2/M phase cell cycle arrest by carnosol and carnosic acid is associated with alteration of cyclin A and cyclin B1 levels

Nimbolide, an active chemical constituent of Azadirachta indica, reportedly has several physiological effects. Here, we assessed novel anticancer effects of nimbolide against bladder cancer EJ and 5637 cells. Nimbolide treatment inhibited the proliferation of both bladder cancer cell lines with an IC50 value of 3 μM. Treatment of cells with nimbolide induced G2/M phase cell cycle arrest via both Chk2-Cdc25C-Cdc2/cyclin B1-Wee1 pathway and Chk2-p21WAF1-Cdc2/cyclin B1-Wee1 pathway. Nimbolide increased JNK phosphorylation and decreased p38MAPK and AKT phosphorylation. Additionally, nimbolide impeded both wound healing migration and invasion abilities by suppressing matrix metalloproteinase-9 (MMP-9) activity. Finally, nimbolide repressed the binding activity of NF-κB, Sp-1, and AP-1 motifs, which are key transcription factors for MMP-9 activity regulation. Overall, our study indicates that nimbolide is a potential chemotherapeutic agent for bladder cancer.

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Fisetin induces G2/M phase cell cycle arrest by inactivating cdc25C-cdc2 via ATM-Chk1/2 activation in human endometrial cancer cells

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i2.21945 ◽

2015 ◽

Vol 10 (2) ◽

pp. 279 ◽

Cited By ~ 3

Author(s):

Zan-Ying Wang ◽

Wen-Qiong Liu ◽

Si’e Wang ◽

Zeng-Tao Wei

Keyword(s):

Cell Cycle ◽

Endometrial Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Cyclin B1 ◽

Phase Cell ◽

M Cell ◽

Proliferative Effect ◽

Cycle Arrest ◽

M Phase

Endometrial cancer is one of the most prevalent gynaecological malignancies where, currently available therapeutic options remain limited. Recently phytochemicals are exploited for their efficiency in cancer therapy. The present study investigates the anti-proliferative effect of fisetin, a flavonoid on human endometrial cancer cells (KLE and Hec1 A). Fisetin (20-100 µM) effectively reduced the viability of Hec1 A and KLE cells and potentially altered the cell population at G2/M stage. Expression levels of the cell cycle proteins (cyclin B1, p-Cdc2, p-Cdc25C, p-Chk1, Chk2, p-ATM, cyclin B1, H2AX, p21 and p27) were analyzed. Fisetin suppressed cyclin B1 expression and caused inactiva-tion of Cdc25C and Cdc2 by increasing their phosphorylation levels and further activated ATM, Chk1 and Chk2. Increased levels of p21 and p27 were observed as well. These results suggest that fisetin induced G2/M cell cycle arrest via inactivating Cdc25c and Cdc2 through activation of ATM, Chk1 and Chk2.

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Citrate-Induced p85α–PTEN Complex Formation Causes G2/M Phase Arrest in Human Pharyngeal Squamous Carcinoma Cell Lines

International Journal of Molecular Sciences ◽

10.3390/ijms20092105 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2105 ◽

Cited By ~ 1

Author(s):

Kuang-Chen Hung ◽

Shyang-Guang Wang ◽

Meng-Liang Lin ◽

Shih-Shun Chen

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Caspase 3 ◽

Squamous Carcinoma ◽

Cyclin B1 ◽

Phase Cell ◽

Cycle Arrest ◽

Phase Arrest ◽

M Phase

Citrate is a key intermediate of the tricarboxylic acid cycle and acts as an allosteric signal to regulate the production of cellular ATP. An elevated cytosolic citrate concentration inhibits growth in several types of human cancer cells; however, the underlying mechanism by which citrate induces the growth arrest of cancer cells remains unclear. The results of this study showed that treatment of human pharyngeal squamous carcinoma (PSC) cells with a growth-suppressive concentration of citrate caused cell cycle arrest at the G2/M phase. A coimmunoprecipitation study demonstrated that citrate-induced cell cycle arrest in the G2/M phase was associated with stabilizing the formation of cyclin B1–phospho (p)-cyclin-dependent kinase 1 (CDK1) (Thr 161) complexes. The citrate-induced increased levels of cyclin B1 and G2/M phase arrest were suppressed by the caspase-3 inhibitor Ac-DEVD-CMK and caspase-3 cleavage of mutant p21 (D112N). Ectopic expression of the constitutively active form of protein kinase B (Akt1) could overcome the induction of p21 cleavage, cyclin B1–p-CDK1 (Thr 161) complexes, and G2/M phase arrest by citrate. p85α–phosphatase and tensin homolog deleted from chromosome 10 (PTEN) complex-mediated inactivation of Akt was required for citrate-induced G2/M phase cell cycle arrest because PTEN short hairpin RNA or a PTEN inhibitor (SF1670) blocked the suppression of Akt Ser 473 phosphorylation and the induction of cyclin B1–p-CDK1 (Thr 161) complexes and G2/M phase arrest by citrate. In conclusion, citrate induces G2/M phase arrest in PSC cells by inducing the formation of p85α–PTEN complexes to attenuate Akt-mediated signaling, thereby causing the formation of cyclin B1–p-CDK1 (Thr 161) complexes.

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The Antiproliferative Activity of Oxypeucedanin via Induction of G2/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells

Molecules ◽

10.3390/molecules25030501 ◽

2020 ◽

Vol 25 (3) ◽

pp. 501

Author(s):

So Hyun Park ◽

Ji-Young Hong ◽

Hyen Joo Park ◽

Sang Kook Lee

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Antiproliferative Activity ◽

Hepatoma Cells ◽

Phase Cell ◽

Human Hepatoma Cells ◽

Cycle Arrest ◽

Growth Inhibitory Activity ◽

M Phase

Oxypeucedanin (OPD), a furocoumarin compound from Angelica dahurica (Umbelliferae), exhibits potential antiproliferative activities in human cancer cells. However, the underlying molecular mechanisms of OPD as an anticancer agent in human hepatocellular cancer cells have not been fully elucidated. Therefore, the present study investigated the antiproliferative effect of OPD in SK-Hep-1 human hepatoma cells. OPD effectively inhibited the growth of SK-Hep-1 cells. Flow cytometric analysis revealed that OPD was able to induce G2/M phase cell cycle arrest in cells. The G2/M phase cell cycle arrest by OPD was associated with the downregulation of the checkpoint proteins cyclin B1, cyclin E, cdc2, and cdc25c, and the up-regulation of p-chk1 (Ser345) expression. The growth-inhibitory activity of OPD against hepatoma cells was found to be p53-dependent. The p53-expressing cells (SK-Hep-1 and HepG2) were sensitive, but p53-null cells (Hep3B) were insensitive to the antiproliferative activity of OPD. OPD also activated the expression of p53, and thus leading to the induction of MDM2 and p21, which indicates that the antiproliferative activity of OPD is in part correlated with the modulation of p53 in cancer cells. In addition, the combination of OPD with gemcitabine showed synergistic growth-inhibitory activity in SK-Hep-1 cells. These findings suggest that the anti-proliferative activity of OPD may be highly associated with the induction of G2/M phase cell cycle arrest and upregulation of the p53/MDM2/p21 axis in SK-HEP-1 hepatoma cells.

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N-(3'-acetyl-8-nitro-2,3-dihydro-1H,3'H-spiro[quinoline-4,2'-[1,3,4]thiadiazol]-5'-yl) acetamides Induced Cell death in MCF-7 cells via G2/M Phase Cell Cycle Arrest

New Journal of Chemistry ◽

10.1039/d1nj02550c ◽

2022 ◽

Author(s):

Selvaraj Shyamsivappan ◽

Raju Vivek ◽

Thangaraj Suresh ◽

Palanivel Naveen ◽

Kaviyarasu Adhigaman ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Cell Cycle Arrest ◽

Spectroscopic Studies ◽

Phase Cell ◽

X Ray ◽

Cycle Arrest ◽

M Phase ◽

Mcf 7

A progression of new N-(3'-acetyl-8-nitro-2,3-dihydro-1H,3'H-spiro[quinoline-4,2'-[1,3,4]thiadiazol]-5'-yl) acetamide derivatives were synthesized from potent 8-nitro quinoline-thiosemicarbazones. The synthesized compounds were characterized by different spectroscopic studies and single X-ray crystallographic studies. The compounds were...

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Novel Thiadiazoline Spiro Quinoline Analogues Induced Cell death in MCF-7 cells via G2/M Phase Cell Cycle Arrest

10.21203/rs.3.rs-289802/v1 ◽

2021 ◽

Author(s):

Selvaraj Shyamsivappan ◽

Raju Vivek ◽

Thangaraj Suresh ◽

Adhigaman Kaviyarasu ◽

Sundarasamy Amsaveni ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Cell Cycle Arrest ◽

Spectroscopic Studies ◽

Phase Cell ◽

Quinoline Derivatives ◽

Cycle Arrest ◽

M Phase ◽

Mcf 7

Abstract A progression of novel thiadiazoline spiro quinoline derivatives were synthesized from potent thiadiazoline spiro quinoline derivatives . The synthesized compounds portrayed by different spectroscopic studies and single X-ray crystallographic studies. The compounds were assessed for in vitro anticancer properties towards MCF-7 and HeLa cells. The compounds showed superior inhibition action MCF-7 malignant growth cells. Amongst, the compound 4a showed significant inhibition activity, the cell death mechanism was evaluated by fluorescent staining, and flow cytometry, RT-PCR, and western blot analyses. The in vitro anticancer results revealed that the compound 4a induced apoptosis by inhibition of estrogen receptor alpha (ERα) and G2/M phase cell cycle arrest. The binding affinity of the compounds with ERα and pharmacokinetic properties were confirmed by molecular docking studies.

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Abstract 3817: Nitric oxide-donating aspirin induces G2/M phase cell cycle arrest in human cancer cells by regulating phase transition proteins

10.1158/1538-7445.am2012-3817 ◽

2012 ◽

Author(s):

Li Gao ◽

Jennie L. Williams

Keyword(s):

Nitric Oxide ◽

Phase Transition ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Human Cancer ◽

Phase Cell ◽

Human Cancer Cells ◽

Cycle Arrest ◽

M Phase

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A novel 8-nitro quinoline-thiosemicarbazone analogues induces G1/S & G2/M phase cell cycle arrest and apoptosis through ROS mediated mitochondrial pathway

Bioorganic Chemistry ◽

10.1016/j.bioorg.2020.103709 ◽

2020 ◽

Vol 97 ◽

pp. 103709 ◽

Cited By ~ 4

Author(s):

Selvaraj Shyamsivappan ◽

Raju Vivek ◽

Arjunan Saravanan ◽

Thangaraj Arasakumar ◽

Thangaraj Suresh ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Mitochondrial Pathway ◽

Phase Cell ◽

Cycle Arrest ◽

M Phase

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TLC388 Induces DNA Damage and G2 Phase Cell Cycle Arrest in Human Non-Small Cell Lung Cancer Cells

Cancer Control ◽

10.1177/1073274819897975 ◽

2020 ◽

Vol 27 (1) ◽

pp. 107327481989797

Author(s):

Kun-Ming Wu ◽

Chih-Wen Chi ◽

Jerry Cheng-Yen Lai ◽

Yu-Jen Chen ◽

Yu Ru Kou

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Cyclin B1 ◽

Small Cell ◽

Phase Cell ◽

Small Cell Lung ◽

Cycle Arrest ◽

M Phase ◽

G2 Phase ◽

Induced Apoptosis

TLC388, a camptothecin-derivative targeting topoisomerase I, is a potential anticancer drug. In this study, its effect on A549 and H838 human non-small cell lung cancer (NSCLC) cells was investigated. Cell viability and proliferation were determined by thiazolyl blue tetrazolium bromide and clonogenic assays, respectively, and cell cycle analysis and detection of phosphorylated histone H3 (Ser10) were performed by flow cytometry. γ-H2AX protein; G2/M phase-associated molecules ataxia-telangiectasia mutated (ATM), CHK1, CHK2, CDC25C, CDC2, and cyclin B1; and apoptosis were assessed with immunofluorescence staining, immunoblotting, and an annexin V assay, respectively. The effect of co-treatment with CHIR124 (a checkpoint kinase 1 [CHK1] inhibitor) was also studied. TLC388 decreased the viability and proliferation of cells of both NSCLC lines in a dose-dependent manner. TLC388 inhibited the viability of NSCLC cell lines with an estimated concentration of 50% inhibition (IC50), which was 4.4 and 4.1 μM for A549 and H838 cells, respectively, after 24 hours. Moreover, it resulted in the accumulation of cells at the G2/M phase and increased γ-H2AX levels in A549 cells. Levels of the G2 phase–related molecules phosphorylated ATM, CHK1, CHK2, CDC25C, and cyclin B1 were increased in TLC388-treated cells. CHIR124 enhanced the cytotoxicity of TLC388 toward A549 and H838 cells and induced apoptosis of the former. TLC388 inhibits NSCLC cell growth by inflicting DNA damage and activating G2/M checkpoint proteins that trigger G2 phase cell cycle arrest to enable DNA repair. CHIR124 enhanced the cytotoxic effect of TLC388 and induced apoptosis.

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