• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.161-167
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• 2015

These commensal intestinal bacteria can enhance the immune system and aid in nutrient absorption but can also act as opportunistic pathogens. Among these intestinal bacteria, the anaerobic Bacteroides fragilis are divided into enterotoxigenic B. fragilis (ETBF) which secrete the B. fragilis toxin (BFT) and non-enterotoxigenic B. fragilis (NTBF) which do not secrete BFT. ETBF can cause diarrhea and colitis in both humans and livestock but can also be found in asymptomatic individuals. ETBF is predominantly found in patients with inflammatory diarrheal diseases and traveller's diarrhea. Several clinical studies have also reported an increased prevalence of ETBF in human patients with inflammatory bowel disease (IBD), colitis and colorectal cancer. In small animal models (C57BL/6 wild-type mice, germ-free mice, multiple intestinal neoplasia (Min) mice, rabbits and Mongolian gerbils), ETBF have been found to initiate and/or aggravate IBD, colitis and colorectal cancer. BFT induces E-cadherin cleavage in intestinal epithelial cells resulting in loss of epithelial cell integrity. Subsequent activation of the ${\beta}$-catenin pathway leads to increased cellular proliferation. In addition, ETBF causes acute and chronic colitis in wild-type mice as well as enhances tumorigenesis in Min mice via activation of the Stat3/Th17 pathway. Currently, ETBF can be detected using a BFT toxin bioassay and by PCR. Advances in molecular biological techniques such as real-time PCR have allowed both researchers as well as clinicians to rapidly detect ETBF in clinical samples. The emergence of more sensitive techniques will likely advance molecular insight into the role of ETBF in colitis and cancer.

• Journal of Life Science
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• v.25 no.11
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• pp.1255-1264
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• 2015

Cnidium officinale, a traditional herb, has diverse beneficial pharmacological activities, such as anti-inflammatory, antioxidant, anticancer, and antiangiogenesis effects. However, the cellular and molecular mechanisms of apoptosis by C. officinale are poorly defined. The present study investigated the proapoptotic effects of water, ethanol, and methanol extract of C. officinale (WECO, EECO, and MECO, respectively) in human leukemia U937 cells. The antiproliferative activity of EECO was higher than that of WECO and MECO. The antiproliferative effect of EECO treatment in U937 cells was associated with the induction of apoptotic cell death, including increased populations of annexin-V positive cells, the formation of apoptotic bodies, DNA fragmentation, and increased numbers of cells with a loss of mitochondrial membrane potential (MMP, Δψm). EECO-induced apoptotic cell death was associated with upregulation of death receptor 4 (DR4) and down-regulation of cellular inhibitor of apoptosis protein-1 (cIAP-1), Bcl-2, and total Bid. The EECO treatment also induced the proteolytic activation of caspases (-3, -8, and -9), and degradation of caspase-3 substrate proteins, such as poly(ADP-ribose) polymerase (PARP), β-catenin, and phospholipase C-γ1 (PLCγ1). In addition, the EECO treatment effectively activated the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. However, compound C, a specific inhibitor of AMPK, significantly reduced EECO-induced apoptosis. These results indicate that AMPK is a key regulator of apoptosis in response to EECO in human leukemia U937 cells.

• Molecules and Cells
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• v.41 no.9
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• pp.830-841
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• 2018

Recent studies have indicated that microRNAs (miRNAs) play an important role in hepatocellular carcinoma (HCC) progression. In this study, we showed that miR-766-3p was decreased in approximately 72% of HCC tissues and cell lines, and its low expression level was significantly correlated with tumour size, TNM stage, metastasis, and poor prognosis in HCC. Ectopic miR-766-3p expression inhibited HCC cell proliferation, colony formation, migration and invasion. In addition, we showed that miR-766-3p repressed Wnt3a expression. A luciferase reporter assay revealed that Wnt3a was a direct target of miR-766-3p, and an inverse correlation between miR-766-3p and Wnt3a expression was observed. Moreover, Wnt3a up-regulation reversed the effects of miR766-3p on HCC progression. In addition, our study showed that miR-766-3p up-regulation decreased the nuclear ${\beta}-catenin$ level and expression of Wnt targets (TCF1 and Survivin) and reduced the level of MAP protein regulator of cytokinesis 1 (PRC1). However, these effects of miR-766-3p were reversed by Wnt3a up-regulation. In addition, PRC1 upregulation increased the nuclear ${\beta}-catenin$ level and protein expression of TCF1 and Survivin. iCRT3, which disrupts the ${\beta}-catenin-TCF4$ interaction, repressed the TCF1, Survivin and PRC1 protein levels. Taken together, our results suggest that miR-766-3p down-regulation promotes HCC cell progression, probably by targeting the Wnt3a/PRC1 pathway, and miR-766-3p may serve as a potential therapeutic target in HCC.

• 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.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.591-602
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• 2019

Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231. Although G0S2 acts as a direct inhibitor of adipose triglyceride lipase, action of G0S2 in cancer progression is not yet understood. To investigate whether G0S2 affects invasiveness of MDA-MB-231 cells, G0S2 expression was inhibited using siRNA, which led to decreased cell proliferation, migration, and invasion of MDA-MB-231 cells. Consequently, G0S2 inhibition inactivated integrin-regulated FAK-Src signaling, which promoted Hippo signaling and inactivated ERK1/2 signaling. In addition, G0S2 downregulation decreased ${\beta}$-catenin expression, while E-cadherin expression was increased. It was demonstrated for the first time that G0S2 mediates the Hippo pathway and induces epithelial to mesenchymal transition (EMT). Taken together, our results suggest that G0S2 is a major factor contributing to cell survival and metastasis of MDA-MB-231 cells.

• BMB Reports
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• v.48 no.12
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• pp.668-676
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• 2015

Pluripotent stem cells only exist in a narrow window during early embryonic development, whereas multipotent stem cells are abundant throughout embryonic development and are retainedin various adult tissues and organs. While pluripotent stem cell lines have been established from several species, including mouse, rat, and human, it is still challenging to establish stable multipotent stem cell lines from embryonic or adult tissues. Based on current knowledge, we anticipate that by manipulating extrinsic and intrinsic signaling pathways, most if not all types of stem cells can be maintained in a long-term culture. In this article, we summarize current culture conditions established for the long-term maintenance of authentic pluripotent and multipotent stem cells and the signaling pathways involved. We also discuss the general principles of stem cell maintenance and propose several strategies on the establishment of novel stem cell lines through manipulation of signaling pathways.

• Herbal Formula Science
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• v.25 no.3
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• pp.349-362
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• 2017

Objectives : We investigated whether the components of Ailanthus altissima induced apoptotic cell death in Jurkat acute lymphoblastic leukemia (ALL) cells. Methods : Regulation of cell proliferation is a complex process involving the regulated expression and/or modification of discrete gene products, which control transition between different stages of the cell cycle. Results : Upon treatments with Ailanthus altissima, the concentration-dependent inhibitions of cell viability were observed as compared to untreated control group. The capability of Ailanthus altissima to induce apoptosis was associated with proteolytic cleavage of specific target proteins such as poly(ADP-ribose)polymerase (PARP) and beta-catenin proteins suggesting the possible involvement of caspases. Ailanthus altissima also caused apoptosis as measured by cell morphology and DNA fragmentation. Conclusions : These results indicate that the increase of apoptotic cell death by Ailanthus altissima may be due to the inhibition of cell cycle in human Jurkat lymphocytes. Conclusively, these current and further findings will provide novel approaches to understanding and treating major diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2789-2800
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• 2013

Background: The aim of this systematic review was to investigate whether stem cells could be effectively applied in targeted therapy of breast cancer. Material and Method: A systematic literature search was performed for original articles published from January 2007 until May 2012. Results: Nine studies met the inclusion criteria for phase I or II clinical trials, of which three used stem cells as vehicles, two trials used autologous hematopoetic stem cells and in four trials cancer stem cells were targeted. Mesenchymal stem cells (MSCs) were applied as cellular vehicles to transfer therapeutic agents. Cell therapy with MSC can successfully target resistant cancers. Cancer stem cells were selectively targeted via a proteasome-dependent suicide gene leading to tumor regression. $Wnt/{\beta}$-catenin signaling pathway has been also evidenced to be an attractive CSC-target. Conclusions: This systematic review focused on two different concepts of stem cells and breast cancer marking a turning point in the trials that applied stem cells as cellular vehicles for targeted delivery therapy as well as CSC-targeted therapies. Applying stem cells as targeted therapy could be an effective therapeutic approach for treatment of breast cancer in the clinic and in therapeutic marketing; however this needs to be confirmed with further clinical investigations.

• YAKHAK HOEJI
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• v.56 no.6
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• pp.358-363
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• 2012

Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine protein kinase, plays an important role in wide variety of developmental events. NLK phosphorylates T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional complex and suppresses wnt signaling pathway through inhibition of ${\beta}$-catenin/TCF complex interaction. However, the function of NLK in gastric carcinogenesis has not been investigated. In the present study, we have examined whether the NLK gene is involved in the development and/or progression of gastric cancers. NLK expression was analyzed by immunohistochemical staining in 153 advanced gastric cancer specimens. Immunhistochemical analysis showed increased expression of NLK in 91 (59.5%) out of 153 gastric cancer specimens. Statistically, there was no significant relationship between altered expression of NLK protein and clinicopathological parameters, including tumor differentiation, location, lymph node metastasis. We identified that mRNA and protein expression of NLK was significantly up-regulated in human gastric cancer tissues compare to corresponding normal gastric tissues. In addition, we found that human gastric cancer cell lines exhibited relatively high expression of NLK, as compared with normal gastric cells. The results of this study suggest that aberrant regulation of NLK may contribute to the development or progression of gastric cancers and serve as a potential biomarker for advanced gastric cancer patients.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.5
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• pp.649-659
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• 2011

To examine the anti-cancer effects of Lepidium virginicum L., the anti-proliferative and pro-apoptotic effects of a water extract of L. virginicum leaves (WELVL) and of L. virginicum roots (WELVR) were investigated in HCT116 human colon carcinoma cells. The treatment of HCT116 cells with WELVL and WELVR resulted in the inhibition of growth and morphological changes in a concentration-dependent manner by inducing apoptosis. The growth inhibition and apoptosis induction by WELVR was stronger than that of WELVL thus, we determined that WELVR was the more optimal extract for this study. The increased apoptotic events in HCT116 cells caused by WELVR were associated with an up-regulation of Fas ligand, Bax, and Bad expression, a down-regulation of Bcl-2, Bcl-$_XL$, and Bid expression, and a decrease in the mitochondrial membrane potential (MMP, ${\Delta}{\psi}m$). WELVR treatment induced the proteolytic activation of caspase-3, -8, and -9, and the degradation of caspase-3 substrate proteins, such as poly (ADP-ribose) polymerase (PARP), ${\beta}$-catenin, and phospholipase C-${\gamma}1$ (PLC-${\gamma}1$). In addition, apoptotic cell death induced by WELVR was correlated with a down-regulation of inhibitors of the apoptosis protein (IAP) family, such as the X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and cIAP-2. These findings suggest that the WELVR-induced inhibition of cell proliferation is associated with the induction of apoptotic cell death. WELVR may be a potential chemotherapeutic agent for the control of HCT116 human colon carcinoma cells.