• 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.

• BMB Reports
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• v.46 no.12
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• pp.611-616
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• 2013

Luteolin-7-O-glucoside (LUT7G), a flavone subclass of flavonoids, has been found to increase anti-oxidant and anti-inflammatory activity, as well as cytotoxic effects. However, the mechanism of how LUT7G induces apoptosis and regulates cell cycles remains poorly understood. In this study, we examined the effects of LUT7G on the growth inhibition of tumors, cell cycle arrest, induction of ROS generation, and the involved signaling pathway in human hepatocarcinoma HepG2 cells. The proliferation of HepG2 cells was decreased by LUT7G in a dose-dependent manner. The growth inhibition was due primarily to the G2/M phase arrest and ROS generation. Moreover, the phosphorylation of JNK was increased by LUT7G. These results suggest that the anti-proliferative effect of LUT7G on HepG2 is associated with G2/M phase cell cycle arrest by JNK activation.

• Natural Product Sciences
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• v.19 no.2
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• pp.155-159
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• 2013

Honokiol, a naturally occurring neolignan mainly found in Magnolia species, has exhibited a potential anti-proliferative activity in human cancer cells. However, the growth inhibitory activity against hepatocellular carcinoma cells and the underlying molecular mechanisms has been poorly determined. The present study was designed to examine the anti-proliferative effect of honokiol in SK-HEP-1 human hepatocellular cancer cells. Honokiol exerted anti-proliferative activity with cell-cycle arrest at the G0/G1 phase and sequential induction of apoptotic cell death. The cell-cycle arrest was well correlated with the down-regulation of checkpoint proteins including cyclin D1, cyclin A, cyclin E, CDK4, PCNA, retinoblastoma protein (Rb), and c-Myc. The increase of sub-G1 peak by the higher concentration of honokiol ($75{\mu}M$) was closely related to the induction of apoptosis, which was evidenced by decreased expression of Bcl-2, Bid, and caspase-9. Hohokiol was also found to attenuate the activation of signaling proteins in the Akt/mTOR and ERK pathways. These findings suggest that the anti-proliferative effect of honokiol was associated in part with the induction of cell-cycle arrest, apoptosis, and dow-nregulation of Akt/mTOR signaling pathways in human hepatocellular cancer cells.

• YAKHAK HOEJI
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• v.58 no.1
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• pp.33-39
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• 2014

The objective of this study is to evaluate the anticancer effects of the isoflavone extract from Chungkukjang in human breast cancer, MDA-MB-453 cells. For this study, MDA-MB-453 cells were treated with 12.5, 25, and $50{\mu}g$ isoflavone extract for 24, 48, and 72 hr. Cell proliferations were decreased in a time- and dose-dependent manner. Reduced cell proliferation was suspected by apoptosis or cell cycle arrest. Therefore, after treatment of $50{\mu}g$ isoflavone extract, apoptotic cells were investigated by annexin V staining. The results indicated that isoflavone extract increased the number of early apoptotic cells compared with control. Cleaved PARP was also increased. Next, we investigated the cell cycle and related proteins. The isoflavone extract leads to cell cycle arrest at the G2/M phase. Moreover isoflavone extract had influenced cell cycle relate proteins such as cyclin B1, cyclin A, and p21. These results suggest that isoflavone extract from Chungkukjang induce apoptosis and cell cycle arrest at G2/M phase via regulation of cell cycle-related proteins in MDA-MB-453 cells.

• Microbiology and Biotechnology Letters
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• v.29 no.3
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• pp.181-185
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• 2001

The naturally occurring chemical indole-3-carbinol (13C), found in vegetables of the Brassica genus, is a promising anticancer agent that was shown previ- ously to induce a Gl cell cycle arrest of human breast cancer cell lines, independent of estrogen receptor signaling. The anticancer activity of 13C and the possible mechanisms of its action were explored in a human hepatocellular carcinoma cell line, HepG2. Treatment of HepG2 cells with 13C suppressed the growth of the cells. The growth sup- pression caused by 13C ($IC_{50}$/: 444$\mu$M) was found to be partially due to its ability to stop the cell cycle in HepG2 cells. Western blot analysis for the Gl phase artiest demonstrated that the expression-levels of cyclin-dependent kinase (Cdk4, Cdk6) and cyclic D were reduced strongly after treatment of Hep72 cells with 13C (4007M) for 24- 72 hrs. Furthermore, I3C selectively abolished the expression of Cdk6 in a dose- and time-dependent manner, and accordingly, inhibited the phosphorylation of retinoblastoma. Interestingly, after the HepG2 cells reached their max- imal growth arrest, the level of the p21, a well-known Cdk inhibitor, increased significantly. Therefore, it could be considered that the Gl arrest of HepG2 cells treated with 13C was due to the indirect inhibition of Cdk4/6 activities by p21 Western blot analysis for G2/M phase arrest of demonstrated the levels of Cdc2 and cyclin Bl werer reduced dramatically after the treatment of HepG2 cells with 13C ($40\mu$M) for 24-72 hrs. flow cytometry of propidium iodide-stained HepG2 cells revealed that 13C induces a Gl (53%,72hr incubation) and G2 (25%,24hr incubation) cell cycle arrest. Thus, our observations have uncovered a previously undefined antiproliferative pathway for r3C that implicates Cdk4/6 and Cdc2 as a target for cell cycle control in human HepG2 cells. However, the 13C-medi- ated cell cycle arrest and repression of Cdk4/6 production did not affect the apoptotic induction of HepG2 cell.

• Journal of Life Science
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• v.23 no.6
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• pp.832-837
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• 2013

In this study, it was investigated the possible mechanisms by which glutamine deprivation exerts its anti-proliferative action in cultured human prostate carcinoma PC3 cells. Glutamine deprivation resulted in inhibition of growth and G2/M arrest of the cell cycle in a time-dependent manner without apoptosis induction, as determined by MTT assay, DAPI staining and flow cytometry analyses. The induction of G2/M arrest by glutamine deprivation was associated with the inhibition of expression of Cdc2, cyclin A and cyclin B1, and up-regulation of the expression of cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1) in both transcriptional and translational levels. Moreover, glutamine deprivation increased the phosphorylation of checkpoint kinase (Chk)1 and Chk2; however, the levels of Cdc25C phosphorylation were decreased in response to glutamine deprivation in a time-dependent manner. Our data provide a first biochemical evidence that glutamine deprivation suppresses cell viability through G2/M phase arrest without induction of apoptosis in PC3 cells.

• Journal of Microbiology and Biotechnology
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• v.13 no.4
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• pp.607-612
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• 2003

To elucidate the action mechanism of MCS-C2, a novel analogue of toyocamycin and sangivamycin, its effect on the expression of cell cycle-related proteins in the human myelocytic leukemia cell line HL-60 was examined using Western blotting and a flow cytometric analysis. MCS-C2, a selective inhibitor of cyclin-dependent kinases, was found to inhibit cell growth in a time- and dose-dependent manner, and inhibits cell cycle progression by inducing the arrest at G1 and G2/M phases, in HL-60 cells. The flow cytometric analysis revealed an appreciable arrest of cells in the G2/M phase of the cell cycle after treatment with MCS-C2. The HL-60 cell population increased gradually from 13% at 0 h, to 28% at 12 h in the G2/M phase, after exposure to $2{\;}\mu\textrm{M}$ MCS-C2. Furthermore, Western blot analysis demonstrated that MCS-C2 induced the cell cycle arrest at G1 phase through the inhibition of pRb phosphorylation. Hypophosphorylated pRb accumulated after treatment with $5{\;}\mu\textrm{M}$ MCS-C2 for 12 h, whereas, the level of hyperphosphorylated pRb was reduced. Thus, treatment of the cell with MCS-C2 suppressed the hyperphosphorylated form of pRb with a commensurate increase in the hypophosphorylated form.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8313-8319
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• 2016

We have recently shown that thymoquinone (TQ) has a potent cytotoxic effect and induces apoptosis via caspase-3 activation with down-regulation of XIAP in mouse neuroblastoma (Neuro-2a) cells. Interestingly, our results showed that TQ was significantly more cytotoxic towards Neuro-2a cells when compared with primary normal neuronal cells. In this study, the effects of TQ on cell-cycle regulation and the mechanisms that contribute to this effect were investigated using Neuro-2a cells. Cell-cycle analysis performed by flow cytometry revealed cell-cycle arrest at G2/M phase and a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Moreover, TQ increased the expression of p53, p21 mRNA and protein levels, whereas it decreased the protein expression of PCNA, cyclin B1 and Cdc2 in a dose-dependent manner. Our finding suggests that TQ could suppress cell growth and cell survival via arresting the cell-cycle in the G2/M phase and inducing apoptosis of neuroblastoma cells.

• KSBB Journal
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• v.30 no.4
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• pp.175-181
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• 2015

Cells proliferate via repeating process that growth and division. This process is G1, S, G2 and M four phases consists. Monitoring the progression of the cell cycle is a specific step that to be a continuous process is repeated to adjust the start of the next step. At this time, this process is called a Checkpoint. Currently, there are three known checkpoints that G1-S phase, G2-M phase, and the M phase. In this study, we confirmed that cell cycle arrest effects by ethanol extracts of Artemisia annua Linne (AAE) in Hep3B liver cancer cells. AAE was regulated proteins which involved in cell cycle such as pAkt, pMDM2, p53, p21, pCDK2 (T14/Y15). AAE induced cell cycle arrest in G1 checkpoint through phosphorylation of CDK2. Akt and p53 upstream is inhibited by AAE and p53 activated by non-activated pMDM2, p53 inhibitor. Thereby, activated p53 is transcript to p21 and activated p21 protein is combined with Cyclin E-pCDK2 complex. Therefore, we confirmed that AAE-induced cell cycle arrest was occurred by p21-Cyclin E-pCDK2 complex by inhibition of pAkt signal. Because of this cell cycle can't pass to S phase from G1 phase.