• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1555-1563
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• 2007

To idenifty effect of Bojungbangam-tang kakambang on Cisplatin-Induced G2/M Phase Arrest in Human Renal Proximal Tubular HK-2 Cells. Cytotoxicity of cisplatin was detected in HK-2 cells and the value of IC50 is about $25\;{\mu}M$. The treatment of cisplatin to HK-2 showed the G2/M phase cell cycle arrest. The ethanol extract of Bojungbangam-tang kakambang (EBTKB), a new herbal prescription composed of ten crude herbs, inhibited cisplatin-induced G2/M phase arrest in HK-2 cells. EBTKB increased G0/G1 peak in cisplatin-treated HK-2 cells. p53, p21 and p27 expression were increased in cisplatin-treated HK-2 cells. Inhibitory effect of EBTKB on cisplatin-induced G2/M phase arrest was accomplished through inhibition of p53, p21 and p27 expression. Also, reduced CDK2 and cyclin A expression by cisplatin were increased by EBTKB, but cyclin E was not changed. Reduction of ERK activation and increment of p38 activation by cisplatin were increased ERK activation and decreased p38 activation by EBTKB. Cisplatin had no effect on JNK activation, but EBTKB increased JNK activation. These results can suggest that EBTKB inhibits cisplatin-induced G2/M phase arrest in HK-2 cell through reduction of p53-dependent p21 and p27 protein, ERK activation and p38 inactivation.

• YAKHAK HOEJI
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• v.43 no.3
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• pp.378-384
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• 1999

Retinoic acid (RA) and dibutyryl cyclic AMP (dbcAMP) induce the differentiation of the multipotent embryonic carcinoma cell line, F9 cells, into parietal endoderm like cell. The F9 cells are highly proliferative doubling approximately 12 hourse. S Phase is predominant, lasting 10 hours and G2/M phase occupies most of the remaining cycle (2 hours) and G1 phase is nearly non-existent. In this study, we showed the effect of RA and dbcAMPon the cell cycle associated molecules (especially around G1 phase) during F9 cell differentiation. Differentiation of F9 cells was induced by the combined addition of RA ($10^{-7}M$) and dbcAMP (0.5mM), and cells were harvested daily up to 4 days. Flow cytometric analysis showed the prolongation of G1 phase around 30 hours after induction. Western blot analysis revealed that the amount of cyclin D1 and cdk2 were increased at day 4. However, histone H1 kinase activity of cdk2 was decreased. These data strongly suggest that RA and dbcAMP induce the growth arrest of F9 cells at G1 phase by decreasing the activity of cdk2, although they have increased the protein contents of cyclin D1 and cdk2. The reason for the discrepancy between the H1 kinase activity and protein contents are not clear yet.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.119-124
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• 2015

The aim of the present study was to assess whether exposure to the combination of an extremely low frequency magnetic field (ELF-MF; 60 Hz, 1 mT or 2 mT) with a stress factor, such as ionizing radiation (IR) or $H_2O_2$, results in genomic instability in non-tumorigenic human lung epithelial L132 cells. To this end, the percentages of G2/M-arrested cells and aneuploid cells were examined. Exposure to 0.5 Gy IR or 0.05 mM $H_2O_2$ for 9 h resulted in the highest levels of aneuploidy; however, no cells were observed in the subG1 phase, which indicated the absence of apoptotic cell death. Exposure to an ELF-MF alone (1 mT or 2 mT) did not affect the percentages of G2/M-arrested cells, aneuploid cells, or the populations of cells in the subG1 phase. Moreover, when cells were exposed to a 1 mT or 2 mT ELF-MF in combination with IR (0.5 Gy) or $H_2O_2$ (0.05 mM), the ELF-MF did not further increase the percentages of G2/M-arrested cells or aneuploid cells. These results suggest that ELF-MFs alone do not induce either G2/M arrest or aneuploidy, even when administered in combination with different stressors.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.5
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• pp.857-862
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• 2011

The purpose of this study is to investigate the anti-proliferative mechanism by Trichosanthes kirilowii (TCK) in MCF-7 human breast carcinoma cell. In this study, we used human breast cancer cell line, Michigan cancer foundation-7 cells (MCF-7 cells). They were co-incubated with 30~200 ${\mu}g$/ml TCK for 48 hours, and cell viability was measured by Water-soluble tetrazolium salt-1 (WST-1) assay. After MCF-7 cells were exposed to 60 ${\mu}g$/ml of TCK for 0, 3, 6, 12, 24, 48 hours, We performed flow analysis cytometry sorting(FACS) and western blot analysis. We investigated the effect of dose-dependent cell growth inhibition by TCK, which could be proved by WST-1 assay. Also, flow cytometry analysis showed that TCK increased percentage of subG1 phase and G2/M phase cell cycle. In addition, TCK induced apoptosis through the expression of caspase-9, -3 and poly(ADP-ribose) polymerase(PARP) activation. Moreover, we showed that ATM-dependent G2/M phase arrest by DNA damage and phosphorylation of chk2, cdc25C, cdc2(Tyr15). Taken together, these results suggest that by G2/M phase arrest through DNA damage and inducing of apoptosis through intrinsic pathway, TCK may have potential tumor suppressor in breast cancer.

• The Journal of Internal Korean Medicine
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• v.26 no.1
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• pp.48-59
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• 2005

Objectives : The aim of the study was to evaluate the effect of WS on HepG2 cell cycle and expression of related genes. Methods : The MTT assay, Cell counting analysis, $[^3H]-Thymidine$ Incorporation Assay, Flow cytometric analysis, Quantitative RT-PCR were studied. Results : WS inhibited HepG2 cell proliferation in low concentration$(1-10\;{\mu]g/ml)$ which did not cause direct cytotoxicity, with dose-dependant manner. WS in-hibited DNA synthesis as well. Flow cytometric analysis on the HepG2 cell showed G2/M phase arrest. Conclusion : These results suggest that WS inhibits HepG2 cell proliferation not by the gene regulation but by G2/M phase arrest in the cell cycle. Thus further studies on the effect of WS in G2/M phase regulation are thought to be needed.

• Food Science and Preservation
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• v.16 no.5
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• pp.754-758
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• 2009

To develop soybean cake as a functional food material, the anti-oxidative and cytotoxic activities against human colon cancer cells of crude saponins isolated from 70% (v/v) ethanol extracts of cake were investigated. The Diaion HP-20 adsorption method was used for isolation of crude saponins, which were then eluted with 100% ethanol. The non-saponin fraction was removed by elution with $H_2O$ and 20% (v/v) ethanol. The results of thin layer chromatography (TLC) analysis confirmed that crude saponins were present in the 100% ethanol extract of soybean cake. The hydrogen-donating properties of saponins were more than 60% at a concentration of $1,000\;{\mu}g/mL$. malondialdehyde(MDA) production was $1,200\;{\mu}mol\;MDA/g$ in mouse liver homogenate treated with crude saponins at the concentration of $1,000\;{\mu}g/mL$. This value was lower than that of the control, which was $3,700\;{\mu}mol\;MDA/g$. Saponins inhibited the growth of colon cancer cells in a dose- and time-dependent manner. Saponins also resulted in a decrease in the proportion of cells in the G1 phase of the cell cycle, whereas the cell proportion in G2/M phase was increased with $1,000\;{\mu}g/mL$ saponins. Thus, we conclude that saponins may induce G2/M cell cycle arrest.

• Nutrition Research and Practice
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• v.2 no.4
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• pp.322-325
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• 2008

The aim of present study was to investigate the effects of kaempferol on cellular proliferation and cell cycle arrest and explore the mechanism for these effects in human breast carcinoma MDA-MB-453 cells. Cells were treated with kaempferol at various concentrations (ranging from 1 to $200\;{\mu}M$) for 24 and 48 hrs. Kaempferol significantly inhibited cancer cell growth in cells exposed to 50 and $10\;{\mu}M$ of kaempferol and incubated for 24 and 48 hrs, respectively. Exposure to kaempferol resulted in cell cycle arrest at the G2/M phase. Of the G2/M-phase related proteins, kaempferol down-regulated CDK1 and cyclin A and B in cells exposed to kaempferol. In addition, small DNA fragments at the sub-G0 phase were increased by up to 23.12 and 31.90% at 10 and $50\;{\mu}M$ incubated for 24 and 48 hrs, respectively. The kaempferol-induced apoptosis was associated with the up-regulation of p53. In addition, the phosphorylation of p53 at the Ser-15 residue was observed with kaempferol. Kaempferol inhibits cell proliferation by disrupting the cell cycle, which is strongly associated with the induction of arrest at G2/M phase and may induce apoptosis via p53 phosphorylation in human breast carcinoma MDA-MB-453 cells.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.91-98
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• 1998

Purpose : The relationship between environmental PH on the radiation induced-apoptosis in SCK mammary adenocarcinoma cells and cell cycle dependence was investigated. Material and Methods : Mammary adenocarcinoma cells of A/J mice(SCK cells) in exponential growth phase were irradiated with a $l37^Cs$ irradiator at room temperature. The cells were irradiated 1 hour after the media was replaced with fresh media at a different pHs. After incubation at $37^{\circ}C$ for 0-48 h, the extent of apoptosis was determined using agarose gel electrophoresis and flow cytometry. The progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. Bssults : The induction of apoptosis by irradiation in pH 6.6 medium was markedly less than that in pH 7.5 medium. When the cells were irradiated and maintained in pH 7.5 medium, the percentage of cells in $G_2/M$ phase rapidly increased to about $70\%$ at 12 h after an exposure to 120y and returned to control level by 36 h. The percentage of cells in G1 phase decreased as the percentage of cells in $G_2/M$ increased. On the other hand, in pH 6.6 medium the percentage of cells in G2/M phases gradually increased to about $45\%$ at 24 h after 12Gy irradiation and then slowly recessed and consequently, as much as $30-35\%$ of the cells were still in the Ga/M phase 48 h after irradiation. The percentage of cells in G1 phase then increased as the Ga/M arrest began to recede. The radiation-induced Ga/M arrest in PH 0.0 medium lasted markedly longer than that in pH 7.5 medium. Conclusion : Radiation-induced apoptosis in SCK tumor cells are reversely suppressed in an acidic environment. Radiation-induced Ga/M arrest is prolonged in an acidic environment indicating that the suppression of radiation-induced apoptosis and prolongation of radiation-induced Ga/M arrest in an acidic environment are related.

• Environmental Mutagens and Carcinogens
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• v.24 no.3
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• pp.128-136
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• 2004

CYP1A1 is known to be inducible by xenobiotic compouds such as polyciclic aromatic hydrocarbons(PAHs) and 2,3,7,8-tetrachloro-dibenzo-p-dioxin(TCDD). These chemicals have been identified worldwide and can have a significant impact on the human health and well being of human and wildlife. Given these issues, the detection and quantification of these chemicals in biological, environmental and food samples is important. First, we investigated the effect of on CYP1A1 promoter activity, 7-ethoxyresorufin-O-deethylase(EROD) activity and CYP1A1 mRNA expression induced by benzo(k)fluoranthene(B(k)F) in MCF-7 cells. We found that B(k)F significantly up-regulates the level of CYP1A1 prompter activity, EROD and CYP1A1 mRNA. When cells were treated with genistein, it was not changed that EROD and CYP1A1 mRNA, compared to that of control. However, genistein inhibited the B(k)F-induced CYP1A1 promoter activity and mRNA level at high concentration. Furthermore, in this study, effects of HDAC(histone deacetvlase) inhibitors on human prostate cancer cells proliferation were examined. HC-toxin, SAHA and TSA inhibited cell proliferation in PC3 cells. A novel HDAC inhibitor, IN2001 also suppressed the growth of PC3 cells. And IN2001 and SAHA increased S phase and G2/M phase at 12 hrs treatment but cells were arrested G0/G1 phase at 45 hrs treatment. The HC-toxin treatment for 24 hrs and 48 hrs increased G0/G1 at low concentration ($0.1\mu\textrm{m}$) but increased G2/M at more than concentration of $1\mu\textrm{m}$. TSA increased G2/M phase. These findings height the possbility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of prostate cancer.

• Journal of Hydrogen and New Energy
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• v.8 no.3
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• pp.121-129
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• 1997

$ZrV_{0.1}Mn_{0.7}Ni_{1.2}$ alloy ingot (bulk alloy) made by the arc melting was found to be consisting of mostly of $ZrV_{0.2}Mn_{0.98}Ni_{1.04}$ matrix alloy and $ZrV_{0.01}Mn_{0.13}Ni_{1.2}$ 2nd phase alloy. The former alloy had the form of the C15 type Laves alloy structure and the latter one had the intermetallic compound structure of $Zr_9Ni_{11}$. In order to investigate the effect of these two phases on the electrochemical charge-discharge characteristics of bulk $ZrV_[0.1}Mn_0.7}Ni_{1.2}$ alloy, the matrix and the 2nd phase alloys were fabricated separately by arc melting method and their electrochemical characteristics were studied and compared with the bulk alloy. It was found that the discharge capacity was the lowest of 160 mAh/g in the 2nd phase alloy. The matrix alloy exhibited 200 mAh/g. Both were lower than that of the bulk alloy of 250 mAh/g. The matrix and the bulk alloys showed a similar properties in the activation stage, the high rate dischargeability and the self discharge characteristics. Also a signigicant capacity decrease was observed after activation in both alloys. Whereas the 2nd phase alloy showed the very different characteristics. This alloy was found to be difficult to activate. However the capacity was remained constant after the activation. Also the self discharge rate was seen to be better than those of the matrix and the bulk alloys.