• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.92-92
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• 2019

In this study, we evaluated the effect of branch (STB) and leave (STL) extracts from Sageretia thea on ${\beta}$-catenin level in human colorecal cancer cells, SW480 and lung cancer cells, A549. STB and STL dose-dependently suppressed the growth of SW480 and A549 cells. STB and STL decreased ${\beta}$-catenin level in both protein and mRNA level. MG132 decreased the downregulation of ${\beta}$-catenin protein level induced by STB and STL. However, the inhibition of $GSK3{\beta}$ by LiCl or ROS scavenging by NAC did not block the reduction of ${\beta}$-catenin protein by STB and STL. Our results suggested that STB and STL may downregulate ${\beta}$-catenin protein level independent on $GSK3{\beta}$ and ROS. Based on these findings, STB and STL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer and lung cancer.

• Nutrition Research and Practice
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• v.12 no.1
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• pp.3-12
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• 2018

BACKGROUND/OBJECTIVES: Sageretia thea is traditionally used as a medicinal herb to treat various diseases, including skin disorders, in China and Korea. This study evaluated the inhibitory effect of Sageretia thea fruit on melanogenesis and its underlying mechanisms in B16F10 mouse melanoma cells. The active chemical compounds in anti-melanogenesis were determined in Sageretia thea. MATERIALS/METHODS: Solvent fractions from the crude extract were investigated for anti-melanogenic activities. These activities and the mechanism of anti-melanogenesis in B16F10 cells were examined by determining melanin content and tyrosinase activity, and by performing western blotting. RESULTS: The n-hexane fraction of Sageretia thea fruit (HFSF) exhibited significant anti-melanogenic activity among the various solvent fractions without reducing viability of B16F10 cells. The HFSF suppressed the expression of tyrosinase and tyrosinase-related protein 1 (TRP1). The reduction of microphthalmia-associated transcription factor (MITF) expression by the HFSF was mediated by the Akt/glycogen synthase kinase 3 beta ($GSK3{\beta}$) signaling pathway, which promotes the reduction of ${\beta}-catenin$. Treatment with the $GSK3{\beta}$ inhibitor 6-bromoindirubin-3'-oxime (BIO) restored HFSF-induced inhibition of MITF expression. The HFSF bioactive constituents responsible for anti-melanogenic activity were identified by bioassay-guided fractionation and gas chromatography-mass spectrometry analysis as methyl linoleate and methyl linolenate. CONCLUSIONS: These results indicate that HFSF and its constituents, methyl linoleate and methyl linolenate, could be used as whitening agents in cosmetics and have potential for treating hyperpigmentation disorders in the clinic.

• Korean Journal of Plant Resources
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• v.32 no.2
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• pp.109-115
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• 2019

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of branches from Taxillus yadoriki parasitic to Neolitsea sericea (TN-NS-B) against human lung cancer cells, A549. TY-NS-B dose-dependently suppressed the growth of A549 cells. TY-NS-B decreased ${\beta}$-catenin protein level, but not mRNA level in A549 cells. The downregulation of ${\beta}$-catenin protein level by TY-NS-B was attenuated in the presence of MG132. Although TY-NS-B phosphorylated ${\beta}$-catenin protein, the inhibition of $GSK3{\beta}$ by LiCl did not blocked the reduction of ${\beta}$-catenin by TY-NS-B. In addition, TY-NS-B decreased ${\beta}$-catenin protein in A549 cells transfected with Flag-tagged wild type ${\beta}$-catenin or Flag-tagged S33/S37/T41 mutant ${\beta}$-catenin construct. Our results suggested that TN-NS-B may downregulate ${\beta}$-catenin protein level independent on $GSK3{\beta}$-induced ${\beta}$-catenin phosphorylation. Based on these findings, TY-NS-B may be a potential candidate for the development of chemopreventive or therapeutic agents for human lung cancer.

• BMB Reports
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• v.42 no.2
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• pp.119-124
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• 2009

PI(3,4,5)$P_3$ produced by the activated PI3-kinase is a key lipid second messenger in cell signaling downstream of insulin. Skeletal muscle and kidney-enriched inositol phosphatase (SKIP) identified as a 5'-inositol phosphatase that hydrolyzes PI(3,4,5) $P_3$ to PI(3,4)$P_2$, negatively regulates the insulin-induced glycogen synthesis in skeletal muscle. However the mechanism by which this occurs remains unclear. To elucidate the function of SKIP in glycogen synthesis, we employed RNAi techniques to knockdown the SKIP gene in differentiating C2C12 myoblasts. Insulininduced phosphorylation of Akt (protein kinase B) and GSK-3$\beta$ (Glycogen synthase kinase), subsequent dephosphorylation of glycogen synthase and glycogen synthesis were increased by inhibiting the expression of SKIP, whereas the insulin-induced glycogen synthesis was decreased by overexpression of WT-SKIP. Our results suggest that SKIP plays a negative regulatory role in Akt/ GSK-3$\beta$/GS (glycogen synthase) pathway leading to glycogen synthesis in myocytes.

• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.515-525
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• 2023

The most common heart valve disorder is calcific aortic valve stenosis (CAVS), which is characterized by a narrowing of the aortic valve. Treatment with the drug molecule, in addition to surgical and transcatheter valve replacement, is the primary focus of researchers in this field. The purpose of this study is to determine whether niclosamide can reduce calcification in aortic valve interstitial cells (VICs). To induce calcification, cells were treated with a pro-calcifying medium (PCM). Different concentrations of niclosamide were added to the PCM-treated cells, and the level of calcification, mRNA, and protein expression of calcification markers was measured. Niclosamide inhibited aortic valve calcification as observed from reduced alizarin red s staining in niclosamide treated VICs and also decreased the mRNA and protein expressions of calcification-specific markers: runt-related transcription factor 2 and osteopontin. Niclosamide also reduced the formation of reactive oxygen species, NADPH oxidase activity and the expression of Nox2 and p22^phox. Furthermore, in calcified VICs, niclosamide inhibited the expression of β-catenin and phosphorylated glycogen synthase kinase (GSK-3β), as well as the phosphorylation of AKT and ERK. Taken together, our findings suggest that niclosamide may alleviate PCM-induced calcification, at least in part, by targeting oxidative stress mediated GSK-3β/β-catenin signaling pathway via inhibiting activation of AKT and ERK, and may be a potential treatment for CAVS.

• Korean Journal of Plant Resources
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• v.32 no.5
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• pp.442-447
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• 2019

In this study, we evaluated the effect of Rodgersia podophylla leave extracts (RPL) on ${\beta}-catenin$ level in human cancer cells. RPL dose-dependently inhibited cell proliferation in SW480, A549, MDA-MB-231, PC-3 and AsPC-1 cells. RPL dramatically decreased ${\beta}-catenin$ protein level in all cancer cells. However, decreased level of ${\beta}-catenin$ mRNA expression was observed in A549 and AsPC-1 cells. In addition, RPL dramatically attenuated cyclin D1 mRNA expression in all cancer cells. MG132 decreased the downregulation of ${\beta}-catenin$ protein level induced by RPL in all cancer cells, while RPL-induced downregulation of ${\beta}-catenin$ was inhibited by the inhibition of $GSK-3{\beta}$ by LiCl in MDA-MB-231 cells. RPL phosphorylated ${\beta}-catenin$ and $GSK-3{\beta}$. In addition, the inhibition of $GSK-3{\beta}$ by LiCl attenuated RPL-induced ${\beta}-catenin$ phosphorylation. Based on these findings, RPL may be a potential candidate for the development of chemopreventive or therapeutic agents for human cancer.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.108-108
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• 2018

In this study, we evaluated the anti-cancer effect of extracts of leaves (ST-L) and branches (ST-B) from Sageretia theezans in human colorectal cancer cells. ST-L and ST-B significantly inhibited the proliferation of human colorectal cancer cells, SW480. ST-L and ST-B decreased cyclin D1 protein level through the induction of cyclin D1 proteasomal degradation via $GSK3{\beta}$-dependent threonine-286 phosphorylation of cyclin D1. In addition, ST-L and ST-B increased HO-1 protein through p38, ROS and $GSK3{\beta}$-dependent Nrf2 activation. These findings suggest that ST-L and ST-B may have great potential for the development of anti-cancer drug to treat human colorectal cancer.

• Molecules and Cells
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• v.38 no.6
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• pp.506-517
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• 2015

Arabidopsis Shaggy-like protein kinases (ASKs) are Arabidopsis thaliana homologs of glycogen synthase kinase 3/SHAGGY-like kinases (GSK3/SGG), which are comprised of 10 genes with diverse functions. To dissect the function of $ASK{\beta}$ (AtSK32), $ASK{\beta}$ antisense transgenic plants were generated, revealing the effects of $ASK{\beta}$ down-regulation in Arabidopsis. Suppression of $ASK{\beta}$ expression specifically interfered with pollen development and fertility without altering the plants' vegetative phenotypes, which differed from the phenotypes reported for Arabidopsis plants defective in other ASK members. The strength of these phenotypes showed an inverse correlation with the expression levels of $ASK{\beta}$ and its co-expressed genes. In the aborted pollen of $ASK{\beta}$ antisense plants, loss of nuclei and shrunken cytoplasm began to appear at the bicellular stage of microgametogenesis. The in silico analysis of promoter and the expression characteristics implicate $ASK{\beta}$ is associated with the expression of genes known to be involved in sperm cell differentiation. We speculate that $ASK{\beta}$ indirectly affects the transcription of its co-expressed genes through the phosphorylation of its target proteins during late pollen development.

• Korean Journal of Plant Resources
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• v.32 no.2
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• pp.153-159
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• 2019

In this study, we evaluated the effect of branch (STB) and leave (STL) extracts from Sageretia thea on ${\beta}-catenin$ level in human colorecal cancer cells, SW480 and lung cancer cells, A549. STB and STL dose-dependently suppressed the growth of SW480 and A549 cells. STB and STL decreased ${\beta}-catenin$ level in both protein and mRNA level. MG132 decreased the downregulation of ${\beta}-catenin$ protein level induced by STB and STL. However, the inhibition of $GSK3{\beta}$ by LiCl or ROS scavenging by NAC did not block the reduction of ${\beta}-catenin$ protein by STB and STL. Our results suggested that STB and STL may downregulate ${\beta}-catenin$ protein level independent on $GSK3{\beta}$ and ROS. Based on these findings, STB and STL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer and lung cancer.

• Journal of Life Science
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• v.29 no.8
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• pp.871-878
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• 2019

The aim of this study was to determine the anticancer activities of an 80% methanol extract and various fractions of Rhododendron brachycarpum (RB). The n-hexane fraction of RB showed the highest inhibitory activity (Inhibit concentration $50%=20.2{\pm}1.2{\mu}g/ml$) in HT-29 cells. Colony- and sphereforming abilities were significantly correlated with a decrease in the cell count and size. A TOP/FOP flash reporter assay revealed that the inhibitory activity of the n-hexane fraction of RB ($0.22{\pm}0.02$ fold change) was lower than that of the 80% methanol extract and that of other fractions. The n-hexane and ethyl acetate fractions of RB were predominantly dependent on the expression levels of intracellular ${\beta}-catenin$. Western blotting using $p-GSK3{\beta}$ with only the n-hexane fraction of RB was conducted to examine whether these secondary metabolites reduced ${\beta}-catenin$ degradation. Intracellular ${\beta}-catenin$ regulation resulted in quantitative changes in the nucleus. In summary, these results demonstrate the potential of the n-hexane fraction of RB as a natural anticancer agent.