• Microbiology and Biotechnology Letters
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• v.22 no.5
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• pp.495-498
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• 1994

Genistein, a inhibitor of the progression of G$_{1}$ and G$_{2}$ phase of the mammalian cell cycle, was discovered through a unique screening system, in which effects of microbial metabolites on the cycle progression of the cultured mouse mammalian carcinoma cell were monitored by flow cytometry. The inhibitor was extracted from the fermentation broth of Streptomyces sp. ZF10 with ethyl acetate, and purified by silica gel column chromatography and HPLC.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.463-468
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• 2002

We have previously reported on the identification of the endogenous transmethylation inhibitor oligosaccharide-linked acyl carrier protein (O-ACP), In this study, the role of the transmethylation reaction on cell cycle progression was evaluated using various transmethylase inhibitors, including O-ACP. O-ACP significantly inhibited the growth of various cancer cell lines, including NIH3T3, ras-transformed NIH3T3, MDA-MB-231, HT-1376, and AGS. In addition, exposure of ras-transformed NIH3T3 to O-ACP caused cell cycle arrest at the $G_0/G_1$ phase, which led to a decrease in cells at the S phase, as determined by flow cytometry. In contrast, transmethylase inhibitors did not affect the expression of $p21^{WAF1/Cip1}$, a well known inhibitor of cyclin dependent kinase, indicating that the cell cycle arrest by transmethylase inhibitors might be mediated by a $p21^{WAF1/Cip1}$-independent mechanism. Therefore, O-ACP, a novel transmethylase inhibitor, could be a useful tool for elucidating the novel role of methylation in cell proliferation and cell cycle progression.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1655-1659
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• 2016

Celecoxib, a selective inhibitor of COX-2, showed cytotoxic effects in many cancer cell lines including cervical cancer cells. This study investigated the effect of celecoxib on cell cycle arrest in HeLa cervical cancer cells through p53 expression. In vitro anticancer activity was determined with the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method. A double staining method was applied to investigate the mechanism of cell death, cell cycling was analyzed by flow cytometryand immunocytochemistry was employed to stain p53 expression in cells. Celecoxib showed strong cytotoxic effects and induced apoptosis with an $IC_{50}$ value of $40{\mu}M$. It induced cell cycle arrest at G2/M phase by increasing level of p53 expression on HeLa cells.

• International Journal of Contents
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• v.8 no.4
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• pp.74-77
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• 2012

Radiation has been an effective tool for treating cancer for a long time. Radiation therapy induces DNA damage within cancer cells and destroys their ability to reproduce. Radiation therapy is often combined with other treatments, like surgery and chemotherapy. Here, we describe the effects of radiation and histone deacetylase inhibitor, Trichostain A, on cell cycle regulation in hepatoma cells. The combinatorial treatment of radiation and Trichostain A induced cell cycle arrest and thereby increasing the hepatoma cell death. Furthermore, the regulatory effects of radiation and Trichostatin A on cell cycle applied in cell type specifically. These results suggest that the treatment of radiation and Trichostatin A may play a central role in hepatoma cell death and might be a good remedy to improve the efficiency of radiation therapy.

• Proceedings of the Korean Biophysical Society Conference
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• 2001.06a
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• pp.34-34
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• 2001

Survivin, an apoptosis inhibitor/cell-cycle regulator, is critically required for suppression of apoptosis and ensuring normal cell division in the G2/M phase of the cell cycle. It is highly expressed in a cell cycle-regulated manner and localizes together with caspase-3 on microtubules within centrosomes. Whether survivin is a physiologically relevant caspase inhibitor has been unclear due to the difficulties with obtaining correctly folded survivin and finding right conditions for inhibition assay.(omitted)

• Journal of Korean Neurosurgical Society
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• v.66 no.6
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• pp.642-651
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• 2023

Objective : Endothelial colony-forming cells (ECFCs) have been reported to play an important role in the pathogenesis of moyamoya disease (MMD). We have previously observed stagnant growth in MMD ECFCs with functional impairment of tubule formation. We aimed to verify the key regulators and related signaling pathways involved in the functional defects of MMD ECFCs. Methods : ECFCs were cultured from peripheral blood mononuclear cells of healthy volunteers (normal) and MMD patients. Low-density lipoproteins uptake, flow cytometry, high content screening, senescence-associated β-galactosidase, immunofluorescence, cell cycle, tubule formation, microarray, real-time quantitative polymerase chain reaction, small interfering RNA transfection, and western blot analyses were performed. Results : The acquisition of cells that can be cultured for a long time with the characteristics of late ECFCs was significantly lower in the MMD patients than the normal. Importantly, the MMD ECFCs showed decreased cellular proliferation with G1 cell cycle arrest and cellular senescence compared to the normal ECFCs. A pathway enrichment analysis demonstrated that the cell cycle pathway was the major enriched pathway, which is consistent with the results of the functional analysis of ECFCs. Among the genes associated with the cell cycle, cyclin-dependent kinase inhibitor 2A (CDKN2A) showed the highest expression in MMD ECFCs. Knockdown of CDKN2A in MMD ECFCs enhanced proliferation by reducing G1 cell cycle arrest and inhibiting senescence through the regulation of CDK4 and phospho retinoblastoma protein. Conclusion : Our study suggests that CDKN2A plays an important role in the growth retardation of MMD ECFCs by inducing cell cycle arrest and senescence.

• Molecules and Cells
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• v.45 no.12
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• pp.923-934
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• 2022

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have great potential in applications such as regenerative medicine, cardiac disease modeling, and in vitro drug evaluation. However, hPSC-CMs are immature, which limits their applications. During development, the maturation of CMs is accompanied by a decline in their proliferative capacity. This phenomenon suggests that regulating the cell cycle may facilitate the maturation of hPSC-CMs. Aurora kinases are essential kinases that regulate the cell cycle, the role of which is not well studied in hPSC-CM maturation. Here, we demonstrate that CYC116, an inhibitor of Aurora kinases, significantly promotes the maturation of CMs derived from both human embryonic stem cells (H1 and H9) and iPSCs (induced PSCs) (UC013), resulting in increased expression of genes related to cardiomyocyte function, better organization of the sarcomere, increased sarcomere length, increased number of mitochondria, and enhanced physiological function of the cells. In addition, a number of other Aurora kinase inhibitors have also been found to promote the maturation of hPSC-CMs. Our data suggest that blocking aurora kinase activity and regulating cell cycle progression may promote the maturation of hPSC-CMs.

• Journal of Microbiology and Biotechnology
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• v.12 no.3
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• pp.470-475
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• 2002

In the course of screening for a novel cell cycle inhibitor, a potent Cdk 1 inhibitor, HY558, was found from the culture broth of Penicillium minioluteum F558 isolated from a soil sample. The molecular ion of HY558 was identified at m/z 329 (MH+) with a molecular formula of $C_20H_44ON_2$. HY558 exhibited selective antiproliferative effects on various human cancer cell lines. Its $IC_50$ values were estimated to be 0.29 mM on HepG2, 0.30 mM on HeLa, 0.30 mM on HL6O, 0.33 mM on HT-29, and 0.25 mM on AGS cells. Interestingly, Hy558 demonstrated no antiproliferative effect with normal lymphocytes used as the control, and a low level of inhibition on the proliferation of A549 cancer cells. A flow cytometric analysis of HepG2 cells revealed an appreciable arrest of cells at the G1 and G2/M phases of the cell cycle following treatment with Hy558. furthermore, DNA fragmentation due to apoptosis was observed in HeLa cells treated with 0.46 mM of HY558.

• Environmental Analysis Health and Toxicology
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• v.27
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• pp.10.1-10.7
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• 2012

Objectives: In recent years, a number of structurally diverse Histone deacetylase (HDAC) inhibitors have been identified and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. This study aimed at investigating the antitumor activity of newly synthesized HDAC inhibitor, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide (IN-2001) using human breast cancer cells. Methods: We have synthesized a new HDAC inhibitor, IN-2001, and cell proliferation inhibition assay with this chemical in estrogen receptor-positive human breast cancer MCF-7 cells. Cell cycle analysis on MCF-7 cells treated with IN-2001 was carried out by flow cytometry and gene expression was measured by RT-PCR. Results: In MCF-7 cells IN-2001 showed remarkable anti-proliferative effects in a dose- and time-dependent manner. In MCF-7 cells, IN-2001 showed a more potent growth inhibitory effect than that of suberoylanilide hydroxamic acid. These growth inhibitory effects were related to the cell cycle arrest and induction of apoptosis. IN-2001 showed accumulation of cells at $G_2$/M phase and of the sub-$G_1$ population in a time-dependent manner, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with HDAC inhibitor-mediated induction of CDK inhibitor expression. In MCF-7 cells, IN-2001 significantly increased $p21^{WAF1}$ expression. Conclusions: In summary, cyclin-dependent kinase (CDK) induced growth inhibition, possibly through modulation of cell cycle and apoptosis regulatory proteins, such as CDK inhibitors, and cyclins. Taken together, these results provide an insight into the utility of HDAC inhibitors as a novel chemotherapeutic regime for hormone-sensitive and insensitive breast cancer.

• Journal of Life Science
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• v.16 no.5
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• pp.828-833
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• 2006

Maize (Zea mays L.) pistil cell death and stamen cell arrest are pivotal process on the sex determination, which diverges from bisexual state of floral meristem to unisexual state in staminate or pistillate floret. We investigated the temporal and spatial distribution of cell cycle gene expression during maize sex determination. The positive regulatory genes of cell cycle, cyclin A, cyclin B, cyclin dependent kinase (CDK) and Mad2 were highly expressed in the developing pistil and stamen but the expression was disappeared in the dying pistil and arresting stamens. In contrast, the negative regulatory genes of cell cycle, Wee1 and CDK inhibitor (CKI) were expressed in the arresting stamens in the wild-type ear and tasselseed2 mutant tassel, however, these genes were not detected in dying pistil although the cyclin B gene expression was disappeared. These results suggest that both the pistil cell death and stamen cell arrest process in maize sex determination are involved in cell cycle regulation, but the different expression patterns of negative regulatory cell cycle genes in the arresting stamens and aborting pistils suggest that the two processes may have distinctive modes of action.