• Journal of Ginseng Research
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• v.35 no.1
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• pp.45-51
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• 2011

Wild ginseng has been used as a traditional medicine for thousands of years and for increase physical strength in Korea, China and Japan. This study reports that cultivated wild ginseng (CWG) inhibits adipocyte differentiation of 3T3-L1 pre-adipocytes in a concentration-dependent manner. Inhibition of adipocyte differentiation is one possible anti-obesity strategy. CWG inhibits the expression of the adipocyte differentiation regulator peroxisome proliferators-activated receptor (PPAR)${\gamma}$ and CCAAT/enhancer-binding protein ${\alpha}$mRNA. It also inhibited the expression of PPAR${\gamma}$ and adiponectin at the protein level during the differentiation of pre-adipocytes into adipocytes. Additionally, CWG blocked the cell cycle at the sub-$G_1$ phase transition, causing cells to remain in the pre-adipocyte state. These results indicate that CWG inhibits adipocyte differentiation and adipogenesis through pre-adipocyte cell cycle arrest in cultured 3T3-L1 cells.

• Molecules and Cells
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• v.38 no.5
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• pp.457-465
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• 2015

The 15-kDa selenoprotein (Sep15) is a selenoprotein residing in the lumen of the endoplasmic reticulum (ER) and implicated in quality control of protein folding. Herein, we established an inducible RNAi cell line that targets Sep15 mRNA in Chang liver cells. RNAi-induced Sep15 deficiency led to inhibition of cell proliferation, whereas cell growth was resumed after removal of the knockdown inducer. Sep15-deficient cells were arrested at the G1 phase by upregulating p21 and p27, and these cells were also characterized by ER stress. In addition, Sep15 deficiency led to the relocation of focal adhesions to the periphery of the cell basement and to the decrease of the migratory and invasive ability. All these changes were reversible depending on Sep15 status. Rescuing the knockdown state by expressing a silent mutant Sep15 mRNA that is resistant to siRNA also reversed the phenotypic changes. Our results suggest that SEP15 plays important roles in the regulation of the G1 phase during the cell cycle as well as in cell motility in Chang liver cells, and that this selenoprotein offers a novel functional link between the cell cycle and cell motility.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.701-709
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• 2006

The Rhus verniciflua Stokes (乾漆-RVS) has been used in traditional East Asia medicine for the therapy of gastritis, stomach cancer, although the mechanism for the biological activity is unclear. In the present study aims to investigate RVS extract contributes to growth inhibitory effect and it's the molecular mechanism on the human gastric cancer cells. AGS (gastric cancer cells) and RIEI (normal cells) were treated to different concentrations and periods of RVS extract $(10{\;}{\sim{{\;}100{\;}ug/mil)$. Growth inhibitory effect was analyzed by measuring FACS study and MTS assay. Cell cycle inhibition was confirmed by measuring CDK2 kinase activity by immunoprecipitation and kinase assay. And apoptosis was confirmed by surveying caspase cascades activation using a pan caspase inhibitor Exposure to RVS extract (50 ug/mll) resulted in a synergistic inhibitory effect on cell growth in AGS cells. Growth inhibition was related with the inhibition of proliferation and induction of apoptosis. The extract induces Gl -cell cycle arrest through the regulation of cyclins, the induction of p27kip1, and the decrease CDK2 kinase activity. And upregulated p27kip1 level is caused by protein stability increment by the reduction of S-phase kinase-associated protein 2 (Skp2), a key molecule related with p27kip1 ubiquitination and degradation, and do novo protein synthesis. Besides, 乾漆 extract induces apoptosis through the expression of Bax, poly(ADP-ribose) polymerase (PARP) and activation of caspase-3. RVS extract induces Gl -cell cycle arrest via accumulation of p27kip1 and apoptosis in human gastric cancer cells but not in normal cells, therefore we suggest that the extract can be used as a novel class of anti-cancer drugs.

• Journal of Life Science
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• v.19 no.1
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• pp.1-8
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• 2009

In this paper, to elucidate the further mechanisms of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced growth arrest, we investigated the effect of MNNG on cell cycle and proliferation in U937 cells, a p53-null human myeloid leukemia cell line. It was found that MNNG causes an arrest at the G2/M phase of the cell cycle and induces apoptosis, which is closely correlated to inhibition of cyclin B1 and cyelin-dependent kinase (Cdk) 2-associated kinase activities. MNNG treatment in. creased protein and mRNA levels of the Cdk inhibitor p21(WAF1/CIP1), and activated the reporter construct of a p21 promoter. By using p21 promoter deletion constructs, the MNNG-responsive element was mapped to a region between 113 and 61 relative to the transcription start site. These data indicate that in U937 cells MNNG can circumvent the loss of wild-type p53 function and induce critical downstream regulatory events leading to transcriptional activation of p21. Present results indicate that the p53-independent up-regulation of p21 by MNNG is likely responsible for the inhibition of cyclin/Cdk complex kinase activity rather than the down-regulation of cyclins and Cdks expression. These novel phenomena have not been previously described and provide important new insights into the possible biological effects of MNNG.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.255-264
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• 1996

Purpose : Paclitaxel is a chemotherapeutic agent with potent microtubule stabilizing activity that arrests cell cycle in $G_2$-M Because $G_2$-M is the most radiosensitive Phase of the cell cycle, paclitaxel has potential as a cell cycle- specific radiosensitizer. This study was designed to investigate the ability of paclitaxel to increase the radiotoxicity in normal small bowel mucosa of the rat. materials and Methods : A sigle intraperitoneal infusion of paclitaxel (10mg/kg), and a single irradiation(8 Gy, x-ray) to the whole abdomen and combination of radiation(8 Gr, x-ray) 24 hours after paclitaxel infusion in the rats were done. The changes of jejunal mucosa, and kinetics of mitotic arrest and apoptosis in the jejunal crypt were defined at 6 hours - 5 days after each treatment histologically. Results : Paclitaxel blocked jejunal crypt cell in mitosis and induced minmal apoptosis. Mitotic arrest by paclitaxel was peaked at 6 hours after infusion and returned to normal by 24 hours. Radiation induced apoptosis and peaked at 6 hours and returned to normal by 24 hours. Combination of paclitaxel and radiation blocked crypt cell in mitosis at 3 days and induced apoptosis slightly at 6 hours and 24 hours and returned to normal by 3 days. The incidence of apoptosis in combined group at 6 hours was slightly higher than normal control but significantly lower than radiation alone group. The major changes of jejunal mucosa were nuclear vesicle and atypia which were appeared at 6 hours - 3 days and returned to normal by 5 days The degree of the mucosal changes are not different in 3 groups except for absence of inflmmatory reaction in radiation group. Conclusion : Mitotic arrest by paclitaxel was peaked at 6 hours and returned to normal by 24 hours and paclitaxel induced minimal apoptosis. Radiation induced apoptosis, peaked at 6 hours and returned to normal by 24 hours. Radiation-induced apoptosis was less in combined group which suggested that paclitaxel have a radioprotective effect when radiation was given 24 hours after paclitaxel infusion.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.275-284
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• 2002

Background : Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. Methods : A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. Results : Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. Conclusion : Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene, Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.

• Journal of Life Science
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• v.23 no.9
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• pp.1109-1117
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• 2013

Induction of G1 Arrest by Methanol Extract of Lycopus lucidus in Human Lung Adenocarcinoma A549 Cells Lycopus lucidus, a herbaceous perennial, is used as a traditional remedy in East Asia, including China and Korea. It has been reported that L. lucidus has anti-allergic effects, inhibitory effects on cholesterol acyltransferase in high glucose-induced vascular inflammation, and anti-proliferative effects in human breast cancer cells. However, the molecular mechanisms of the anti-cancer effects of L. lucidus have not yet been fully determined. In this study, we evaluated the anti-cancer effect and the mechanism of action of L. lucidus in human lung adenocarcinoma A549 cells using methanol extracts of L. lucidus (MELL). MELL treatment showed cytotoxic activity in a dose-dependent manner and induced G1 arrest in A549 cells. The induction of G1 arrest by MELL was associated with the up-regulation of phospho-CHK2 and the down-regulation of Cdc25A phosphatase. In addition, MELL treatment induced decreased expression of G1/S transition-related proteins, including CDK2, CDK4, CDK6, cyclin D1 and cyclin E. MELL also regulated the mRNA expression of CDK2 and cyclin E. On the other hand, the expression of p53 and the cyclin-dependent kinase inhibitor p21 was not induced by MELL. Collectively, these results suggest that MELL may exert an anti-cancer effect by cell cycle arrest at G1 phase through the ATM/CHK2/Cdc25A/CDK2 pathway in A549 cells.

• Korean Journal of Microbiology
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• v.44 no.4
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• pp.299-304
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• 2008

Monocytic cells in myeloid lineage are known for latent site of HCMV Previous studies have suggested that HCMV regulates cell cycle progression in a variety of cells, but studies in monocytic cells are limited. In this study, we attempted to understand cell cycle changes after HCMV infection in the monocytic cell lines. Flow cytometric analyses using propidium iodide revealed that the proportion of G0-G1 phase was increased and the proportion of S phase decreased in HCMV-infected THP-1 cells, but not in HL-60 cells. BrdU-incorporation assay supported that cell proliferation was inhibited in HCMV-infected THP-1 cells by inhibition of de novo DNA synthesis. Western blot analysis revealed that p21, inhibitor of cell cycle progression from G1 phase to S phase, was induced in HCMV-infected THP-1 cells but not in HL-60 cells. Thus, HCMV inhibited cell pro-liferation by arresting the cell cycle at G0-G1 phase through induction of p21 protein in promocytic THP-1 cells.

• Microbiology and Biotechnology Letters
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• v.42 no.1
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• pp.73-81
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• 2014

Salsola collina, also known as Russian thistle, is widely distributed in and around waste facilities, roadsides, and drought and semi-drought areas, and is used as a traditional folk remedy in Chinese medicine for the treatment of hypertension. In this study, we have evaluated the anti-oxidative and anti-cancer activities of the ethanol extract of S. collina Pall. (EESC), and the molecular mechanisms of its anti-cancer effects on human colon carcinoma HT29 cells. EESC exhibited anti-oxidative activity through DPPH radical scavenging capacity and showed cytotoxic activity in a dose-dependent manner in HT29 cells. After EESC treatment, HT29 cells altered their morphology, becoming smaller and irregular in shape. EESC also induced cell accumulation in the G2/M phase in a dose-dependent manner, accompanied by a decrease of cell population in the G1 phase. The G2/M arrest by EESC was associated with the increased expression of cyclin-dependent kinase (CDK) inhibitor p21 and Wee1 kinase, which phosphorylates, or inactivates, Cdc2. EESC treatment induced the phosphorylation of Cdc2 and Cdc25C, and inhibited cyclin A and Cdc25C protein expression. In addition, S arrest was induced by the highest concentration of EESC treatment, associated with a decrease of cyclin A and Cdk2 expression. These findings suggest that EESC may possess remarkable anti-oxidative activity and exert an anti-cancer effect in HT29 cells by cell cycle regulation.

• Journal of Life Science
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• v.29 no.6
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• pp.679-687
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• 2019

Litsea populifolia, a plant species of the Lauraceae family, is widely distributed in the tropical and subtropical areas of Asia. The phylogenetic relationships and botanical characteristics of L. populifolia have been reported; however, its anti-oxidative and anti-cancer activities remain unclear. In this study, we evaluated the anti-oxidative and anti-cancer effects of ethanol extracts of L. populifolia (EELP) together with the molecular mechanism of its anti-cancer activity in human lung adenocarcinoma A549 cells. EELP showed significant anti-oxidative effects with a 50% inhibitory concentration at $11.71{\mu}g/ml$, which was measured by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. EELP exhibited cytotoxic activity and induced cell cycle arrest at the G1 phase in A549 cells in a dose-dependent manner, whereas EELP did not have the cytotoxic effect on the normal human lung cell line IMR90. Treatment with EELP also resulted in a decreased expression of G1/S transition-related molecules-including cyclin-dependent kinase (CDK) 2, CDK6, cyclin D1, and cyclin E-both for the transcription and translation levels. EELP-induced G1 arrest was associated with the phosphorylation of checkpoint kinase 2 (CHK2), p53, cell division cycle 25 homolog A (CDC25A), and the reduction of CDC25A expression in A549 cells. Collectively, these results suggest that EELP may exert an anti-cancer effect by cell cycle arrest at the G1 phase through both p53-dependent and p53-independent (ATM/CHK2/CDC25A/CDK2) pathways in A549 cells.