• Bulletin of the Korean Chemical Society
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• 제30권6호
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• pp.1313-1316
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• 2009

Cdc25 phosphatases have been considered as attractive drug targets for anticancer therapy due to the correlation of their overexpression with a wide variety of cancers. We have been able to identify five novel Cdc25 phosphatase inhibitors with micromolar activity by means of a structure-based de novo design method with a known inhibitor scaffold. Because the newly discovered inhibitors are structurally diverse and have desirable physicochemical properties as a drug candidate, they deserve further investigation as anticancer drugs. The differences in binding modes of the identified inhibitors in the active sites of Cdc25A and B are addressed in detail.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3881-3885
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• 2016

Background: MicroRNAs (miRNAs) have fundamental roles in tumorigenesis. MiR-675 is upregulated in hepatocellular carcinoma(HCC) cells. However, the roles of miR-675 in hepatocellular carcinogenesis are still not fully elucidated. In this study, we focus on investigating the effect and mechanism of miR-675 in proliferation of HCC cells. Materials and Methods: The cell proliferation was measured by MTT assays after transfection with miR-675 inhibitor and miR-675 mimics in HCC cells. The expression level of miR-675 was detected by real-time quantitative reverse transcription polymerase chain reaction. Protein expression of Cdc25A was measured by western blotting analysis. Results: In MTT assays, overexpression of miR-675 promoted the proliferation of HCC cells(P<0.05. at 48 hours, P<0.01. at 72 hours) compared with the miR-675mimics control group. Downexpression of miR-675 inhibited the proliferation of HCC cells(P<0.05. at 48 hours, P<0.01. at 72 hours) compared with the miR-675inhibitor control group. In western blotting analysis, the expression level of Cdc25A was significantly increased (p<0.05) after treatment with miR-675 mimics. The expression level of Cdc25A was significantly decreased (p<0.05) after treatment with miR-675 inhibitor. Conclusions: Our results indicate that miR-675 promotes the proliferation in human hepatocellular carcinoma cells by associating with Cdc25A signaling pathway.

• Asian-Australasian Journal of Animal Sciences
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• 제22권6호
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• pp.781-787
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• 2009

The sense and antisense digoxigenin-labeled RNA probes of four genes, Cdc25A, Cdc25B, Sox2 and Mnb, were produced by using SP6 and T7 RNA polymerases, respectively, and in vitro transcription. Expression patterns of the four genes were detected by in situ hybridization in HH (Hamburger and Hamilton) stage 10 chick embryos. In general, expression patterns of the four genes were similar. mRNA of the four genes was mostly restricted to the entire CNS (central nervous system). All were confined to an identical region, neural tube, neural groove and caudal neural plate, corresponding to the notochord or spinal cord, but there was some distinction in specific region or in concentration, for example in somites. The overlap in expression at the same developmental stage in the CNS suggests that the four genes may be functional similar or related in CNS development. Expression patterns of the four genes support specific roles of these regulators in the developing CNS.

• 한국미생물·생명공학회지
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• 제42권1호
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• pp.73-81
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• 2014

본 연구에서는 명아주과 수송나물속 솔장다리(Salsola collina Pall.) 추출물의 항산화 및 항암 활성을 분석하였다. 먼저 솔장다리의 에탄올 추출물의 DPPH radical scavenging activity를 분석한 결과, $IC_{50}$가 $4.82{\mu}g/ml$로 나타나 강한 항산화능을 보유하였음을 확인하였다. 또한 대장암 세포주(HT29), 폐암 세포주(A549), 간암 세포주(HepG2)를 사용하여 솔장다리 추출물의 암세포 사멸효과를 분석한 결과, $IC_{50}$가 각각 43.8, 64.1, $92.5{\mu}g/ml$로 강력한 세포사멸효과를 나타냈으며 특히 HT29에 대한 강한 사멸효과를 보였다. 솔장다리 추출물의 항암 활성 기전 분석을 위해 세포주기를 분석한 결과, 대장암세포인 HT29의 G2/M arrest를 유도하였으며 최고 농도인 $60{\mu}g/ml$까지 S기 세포수가 증가하였다. 세포주기관련 단백질의 발현 분석 결과, 솔장다리 추출물을 처리한 경우, G2기에서 M기로의 전이에 필수적인 단백질인 Cdc25C와 cyclin A의 발현이 감소되었고, 반면 Cdc25C와 Cdc2의 불활성화 형태인 p-Cdc25C, p-Cdc2는 증가하였다. 또한 p21과 Wee1의 발현도 증가되었다. 하지만 p53의 발현량은 변화가 없었다. 이러한 결과는 솔장다리 추출물을 처리한 경우, p53 비의존적으로 p21의 발현이 증가되어 cyclin A/Cdc2 complex의 활성이 조절되고, 이어서 G2/M phase의 check point에 작용하는 Wee1의 발현증가 및 Cdc25C, Cdc2의 인산화에 의한 불활성화를 통하여 G2/M arrest가 유도되는 것을 시사한다. 또한 솔장다리 추출물 처리에 의해 S기 진행을 조절하는 Cdk2의 발현량도 감소하여, cyclin A/Cdk2 complex가 감소되어 S기의 세포수가 증가한 것으로 보인다. 따라서 본 연구 결과를 통해 솔장다리 추출물이 높은 항산화 활성을 지니며 암세포의 세포주기를 조절하여 높은 항암 활성을 보유함을 확인하였다.

• Journal of Ginseng Research
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• 제48권1호
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• pp.40-51
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• 2024

Background: Ginsenoside 20(S)-Rg3 shows promising tumor-suppressive effects in ovarian cancer via inhibiting NF-kB signaling. This study aimed to explore the downstream tumor suppressive mechanisms of ginsenoside Rg3 via this signaling pathway. Materials and methods: A systematical screening was applied to examine the expression profile of 41 kinesin family member genes in ovarian cancer. The regulatory effect of ginsenoside Rg3 on KIF20A expression was studied. In addition, we explored interacting proteins of KIF20A and their molecular regulations in ovarian cancer. RNA-seq data from The Cancer Genome Atlas (TCGA) was used for bioinformatic analysis. Epithelial ovarian cancer cell lines SKOV3 and A2780 were used as in vitro and in vivo cell models. Commercial human ovarian cancer tissue arrays were used for immunohistochemistry staining. Results: KIF20A is a biomarker of poor prognosis among the kinesin genes. It promotes ovarian cancer cell growth in vitro and in vivo. Ginsenoside Rg3 can suppress the transcription of KIF20A. GST pull-down and co-immunoprecipitation (IP) assays confirmed that KIF20A physically interacts with BTRC (β-TrCP1), a substrate recognition subunit for SCF^β-TrCP E3 ubiquitin ligase. In vitro ubiquitination and cycloheximide (CHX) chase assays showed that via interacting with BTRC, KIF20A reduces BTRC-mediated CDC25A poly-ubiquitination and enhances its stability. Ginsenoside Rg3 treatment partly abrogates KIF20A overexpression-induced CDC25A upregulation. Conclusion: This study revealed a novel anti-tumor mechanism of ginsenoside Rg3. It can inhibit KIF20A transcription and promote CDC25A proteasomal degradation in epithelial ovarian cancer.

• Animal cells and systems
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• 제11권1호
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• pp.9-15
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• 2007

The naphthoquinone analog (2,3-dichloro-6,9-dihydroxy-1,4-naphtoquinone, NA) has an inhibitory effect on cdc25A protein phosphatase in vitro, which is responsible for G1/S transition during cell cycle. However, the exact mechanism inducing the growth inhibition is not understood. In this study, we investigated the regulatory mechanisms of growth arrest induced by NA, as a new potent inhibitor of cdc25A phosphatase, in human hepatocarcinoma SK-hep-1 cells. We found that NA induced the G1 arrest by perturbation of protein tyrosine dephosphorylation of Cdk2, which may be resulting from inhibition of cdc25A phosphatase. In addition, p21 was expressed in a p53-independent manner and participated in the NA-induced G1 arrest by inhibiting Cdk2 activity. Although the exact mechanism is not known, the p21 expression might be related to MAPK activation. From these results, we suggest that NA induces G1 arrest via inhibition of cdc25A and induction of p53-independent p21 expression in SK-Hep-1 cells.

• 한국정밀공학회지
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• 제25권3호
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• pp.73-82
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• 2008

Recently MR CDC damper has been applied to semi-active suspension control system gradually. Compared to former hydraulic CDC damper, it has rapid time response performance as well as simple internal structure and wide range of damping force. In order to develop control logic algorithm which enables to take maximum advantage of unique characteristics of MR CDC damper, it is inevitable to perform a thorough investigation into its nonlinear performance. In many previous researches, MR fluid model was either simply assumed as Bingham Plastic, or a phenomenological model based on experiment was established instead to predict damping performance of MR CDC damper. These experimental flow model which is not based on flow analysis but intentionally built to fit damping characteristics, may lead to totally different results in case of different configuration or structure of MR CDC damper. In this study, a generalized flow formula from mathematical flow model of MR fluid for annular orifice is derived to analyze and predict damping characteristics when current is excited at piston valve.

• BMB Reports
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• 제44권8호
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• pp.553-557
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• 2011

We previously reported that CDK2/Cyclin A can phosphorylate and activate the transcription factor NF-Y. In this study, we investigated a potential regulatory role for NF-Y in the transcription of Cyclin A and other cell cycle regulatory genes. Gel-shift assays demonstrate that NF-Y binds to CCAAT sequences in the Cyclin A promoter, as well as to those in the promoters of cell cycle G2 regulators such as CDC2, Cyclin B and CDC25C. Furthermore, expression of Cyclin A increases NF-Y's affinity for CCAAT sequences in the CDC2 promoter; however, Cyclin A's induction of CDC2 transcription is antagonized by p21, an inhibitor of CDK2/Cyclin A. These results suggest a model wherein NF-Y binds to and activates transcription from the Cyclin A promoter, increasing cellular levels of Cyclin A/CDK2 and potentiating NF-Y's capacity for transcriptional transactivation, and imply a positive feedback loop between NF-Y and Cyclin A/CDK2. Our findings are additionally indicative of a role for Cyclin A in activating Cyclin B/CDK1 through promoting NF-Y dependent transcription of Cyclin B and CDC2; NF-Y mediated crosstalk may therefore help to orchestrate cell-cycle progression.

• 통합자연과학논문집
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• 제11권1호
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• pp.25-29
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• 2018

Protein phosphatase manganese dependent 1D (PPM1D), a Ser/Thr protein phosphatise, play major role in the cancer tumorigenesis of various tumors including neuroblastoma, pancreatic adenocarcinoma, medulloblastoma, breast cancer, prostate cancer and ovarian cancer. Hence, analysis on the structural features required for the formation of PPM1D-inhibitor complex becomes essential. In this study, we have performed molecular docking of SL-175 and -176 and protein-protein docking of CDC5L with PPM1D. On analysing the docked complexes, we have identified the important residues involved in the formation of protein-ligand complex. Research concentrating on these residues could be helpful in understanding the pathophysiology of various tumors related to PPM1D.

• 동의생리병리학회지
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• 제18권5호
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• pp.1449-1455
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• 2004

Bufonis venenum (dried toad venom; Chinese name, Chan su) is a traditional Chinese medicine obtained from the skin venom gland of the toad. It has long been used in treating arrhythmia and other heart diseases in China and other Asian countries. Additionally, Bufonis venenum has been reported to selectively inhibit the growth of various lines of human cancer cells. In the present study, it was examined the effects of extract of Bufonis venenum (EBV) on the growth of human bladder carcinoma cell line T24 in order to investigate the anti-proliferative mechanism and induction of apoptosis by EBV. Treatment of T24 cells to EBV resulted in the growth inhibition, morphological change and induction of apoptotic cell death in a dose-dependent manner. Flow cytometric analysis revealed that EBV treatment caused G2/M phase arrest of the cell cycle and down-regulation of cyclin A, cyclin B1 and Cdc2, which was associated with a marked up-regulation of cyclin-dependent kinases (Cdks) inhibitor p21 (WAF1/CIP1) in a p53-independent manner. The Cdc25C expression was also significantly inhibited by EBV treatment, however Wee1 kinase expression was not affected. The induction of apoptotic cell death by EBV was connected with down-regulation of anti-apoptotic Bcl-XS/L expression without alteration pro-apoptotic Bax expression. Taken together, these findings suggest that EBV may be a potential chemotherapeutic agent for the control of human bladder carcinorma cells and further studies will be needed to identify the active compounds that confer the anti-cancer activity of EBV.