• Bulletin of the Korean Chemical Society
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• v.29 no.9
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• pp.1659-1660
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• 2008

• Bulletin of the Korean Chemical Society
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• v.25 no.12
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• pp.1755-1756
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• 2004

• Bulletin of the Korean Chemical Society
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• v.35 no.1
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• pp.319-321
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• 2014

• Bulletin of the Korean Chemical Society
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• v.30 no.6
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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.

• Molecules and Cells
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• v.27 no.3
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• pp.345-350
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• 2009

We previously reported that flavone induces embryonic lethality in Caenorhabditis elegans, which appeared to be the result of cell cycle arrest during early embryogenesis. To test this possibility, here we examined whether flavone inhibits the activity of a key cell cycle regulator, CDC-25.1 in C. elegans. A gain-of-function cdc-25.1 mutant, rr31, which exhibits extra cell divisions in intestinal cells, was used to test the inhibitory effects of flavone on CDC-25 activity. Flavone inhibited the extra cell divisions of intestinal cells in rr31, and modifications of flavone reduced the inhibitory effects. The inhibitory effects of flavone on CDC-25.1 were partly, if not completely, due to transcriptional repression.

• Journal of Integrative Natural Science
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• v.11 no.1
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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.

• Animal cells and systems
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• v.11 no.1
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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.

• Bulletin of the Korean Chemical Society
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• v.25 no.8
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• pp.1121-1122
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• 2004

• 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.

• Microbiology and Biotechnology Letters
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• v.41 no.4
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• pp.425-432
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• 2013

Typha orientalis, also known as bulrush or cattail, is a perennial herbaceous plant found in freshwater wetlands and has been widely used in constructed wetlands for wastewater treatment. Recent data has revealed that SH21B, a mixture composed of seven herbs including T. orientalis, exhibited an anti-adipogenic activity by the inhibition of the expression of adipogenic regulators. However, the anti-cancer effect of T. orientalis and its molecular mechanisms remain unclear. In this study, we evaluated the anti-cancer effect and its mechanism in the methanol extract of T. orientalis (METO) on human colon carcinoma HT29 cells. It was found that METO treatment showed cytotoxic activity in a dose-dependent manner, and induced G2/M cell cycle arrest and apoptosis in HT29 cells. The induction of G2/M arrest by METO was associated with the up-regulation of phospho-Cdc2 (Tyr15), an inactive form of Cdc2 and the down-regulation of Cdc25c phosphatase. METO also induced tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) expression. In addition, METO-induced apoptosis was characterized by the proteolytic activation of caspase-3, degradation of poly ADP ribose polymerase (PARP), and up-regulation of death receptor FAS and pro-apoptotic Bax expression. Collectively, these results indicate that the cell cycle inhibition and apoptosis induction of METO in HT29 cells allows for the possibility of its use in anti-cancer therapies.