• Journal of Acupuncture Research
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• v.20 no.3
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• pp.45-62
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• 2003

Objective : To examine the effects of Beevenom on the cell proliferation of human breast carcinoma cell line MCF-7, we performed various experiments such as does-dependent effect of Beevenom on cell proliferation and viability, morphological changes, and alterations of apoptosis/cell cycle-regulatory gene products. Methods : Beevenom induced cell viability and proliferation of MCF-7 cells in a concentration-dependent manner. The anti-proliferative effect by Beevenom treatment in MCF-7 cells was associated with morphological changes such as membrance shrinking and cell rounding up. Results : Beevenom induced apoptotic cell death in a concentration-dependent manager, which was associated with degradation of ${\beta}$-catenin, an apoptotic target protein. Beevenom induced the Bax expressions, a pro-apoptotic gene, both in protein and mRNA levels, however, the levels of Bcl-$X_{S/L}$ expression, an anti-apoptotic gene, were down-regulated in Beevenom-treated cells. Western blot analysis and RT-PCT data revealed that the levels of cyclin of B1 protein and cyclin E mRNA were reduced by Beevenom treatment in MCF-7 cells, respectively, where as the expression of tumor suppressor p53 and cyclin dependent kinase inhibitor p21 mRNA were markedly increased in a concentration-dependent fashion. Conclusions : Taken together, these findings suggest that Beevenom induced inhibition of human breast cancer cell proliferation is associated with the induction of apoptotic cell death and Beevenom may have therapeutic potential in human breast cancer.

• Journal of Microbiology and Biotechnology
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• v.28 no.10
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• pp.1645-1653
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• 2018

The genus Acer contains several species with various bioactivities including antioxidant, antitumor and anti-inflammatory properties. However, Acer okamotoanum Nakai, one species within this genus has not been fully studied yet. Therefore, in this study, we investigated the anti-adipogenic activities of leaf extract from A. okamotoanum Nakai (LEAO) on 3T3-L1 preadipocytes. Adipogenesis is one of the cell differentiation processes, which converts preadipocytes into mature adipocytes. Nowadays, inhibition of adipogenesis is considered as an effective strategy in the field of anti-obesity research. In this study, we observed that LEAO decreased the accumulation of lipid droplets during adipogenesis and down-regulated the expression of key adipogenic transcription factors such as peroxisome proliferator-activated receptor ${\gamma}$ (PPAR ${\gamma}$) and CCAAT/enhancer binding protein ${\alpha}$ (C/EBP ${\alpha}$). In addition, LEAO inactivated PI3K/Akt signaling and its downstream factors that promote adipogenesis by inducing the expression of PPAR ${\gamma}$. LEAO also activated ${\beta}$-catenin signaling, which prevents the adipogenic program by suppressing the expression of PPAR ${\gamma}$. Therefore, we found that treatment with LEAO is effective for attenuating adipogenesis in 3T3-L1 cells. Consequently, these findings suggest that LEAO has the potential to be used as a therapeutic agent for preventing obesity.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.555-566
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• 2018

Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs co-culture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the co-localization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and ${\beta}-catenin$; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.4
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• pp.299-310
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• 2020

Alzheimer's disease (AD) is a multi-faceted neurodegenerative disease. Thus, current therapeutic strategies require multitarget-drug combinations to treat or prevent the disease. At the present time, single drugs have proven to be inadequate in terms of addressing the multifactorial pathology of AD, and multitarget-directed drug design has not been successful. Based on these points of views, it is judged that combinatorial drug therapies that target several pathogenic factors may offer more attractive therapeutic options. Thus, we explored that the combination therapy with lower doses of cilostazol and aripiprazole with add-on donepezil (CAD) might have potential in the pathogenesis of AD. In the present study, we found the superior efficacies of donepezil add-on with combinatorial mixture of cilostazol plus aripiprazole in modulation of expression of AD-relevant genes: Aβ accumulation, GSK-3β, P300, acetylated tau, phosphorylated-tau levels, and activation of α-secretase/ADAM 10 through SIRT1 activation in the N2a Swe cells expressing human APP Swedish mutation (N2a Swe cells). We also assessed that CAD synergistically raised acetylcholine release and choline acetyltransferase (CHAT) expression that were declined by increased β-amyloid level in the activated N2a Swe cells. Consequently, CAD treatment synergistically increased neurite elongation and improved cell viability through activations of PI3K, BDNF, β-catenin and α7-nicotinic cholinergic receptors in neuronal cells in the presence of Aβ_1-42. This work endorses the possibility for efficient treatment of AD by supporting the synergistic therapeutic potential of donepezil add-on therapy in combination with lower doses of cilostazol and aripiprazole.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.451-456
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• 2003

We investigated the effects of Sabaek-san (SBS) water extract on the growth of human lung carcinoma A549 cells. Upon treatment with SBS extract, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis. including condensation of chromatin. Flow cytometry analysis confirmed that SBS treatment increased populations of apoptotic-sub G1 phase. In addition. proteolytic cleavages of poly(ADP-ribose) polymerase and β-catenin protein were observed after treatment of SBS extract. These apoptotic effects of SBS in A549 cells were associated with marked inhibition of Bcl-2 and Bel-xL mRNA in a dose-dependent manner. however the levels of Bax expression were not affected, SBS treatment also induced a proteolytic activation of caspase-3. which is believed to play a central role In the apoptotic signaling pathway. The previous and present results indicated that SBS-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1/S progression and the induction of apoptosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.630-641
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• 2008

Gamisamgibopae-tang (GMSGBPT) is a traditional Korean medicine, which has been used for patients suffering from a lung disease in Oriental medicine. In the present study, we examined the biochemical mechanisms of apoptosis by GMSGBPT in NCI-H460 and A549 human non-small-cell lung cancer cell lines. It was found that GMSGBPT could inhibit the cell proliferation of A549 cells in a concentration-dependent manner, however GMSGBPT did not affect the cell proliferation of NCI-H460 cells. Apoptotic cell death in A549 cells were detected using DAPI staining and annexin V fluorescein methods. The induction of apoptotic cell death by GMSGBPT was connected with a down-regulation of anti-apoptotic Bcl-2 and Bcl-xL expression, and proteolytic activation of caspase-3 and caspase-9 in A549 cells. However, GMSGBPT did not affect the levels of pro-apoptotic Bax and Bad expression, and activity of caspase-8. GMSGBPT treatment also concomitant degradation and/or inhibition of poly (ADP-ribose) polymerase (PARP), ${\beta}$-catenin, phospholipase C-1 (PLC${\gamma}$1) and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Taken together, these findings suggest that GMSGBPT may be a potential chemotherapeutic agent for the control of human non-small-cell lung cancer cells and further studies will be needed to identify the active compounds that confer the anti-cancer activity of GMSGBPT.

• Korean Journal of Veterinary Research
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• v.54 no.3
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• pp.171-177
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• 2014

Garlic and mugwort have long been used in traditional medicine to prevent various diseases. Several in vitro studies have reported protective efficacies of garlic and mugwort in cases of gastric cancer. In the present study, we investigated the cancer preventive effects of garlic and mugwort mixture extract (GME) in a Helicobacter (H.) pylori-associated gastric carcinogenesis mouse model. To induce gastric cancer, C57BL/6 mice were treated with N-methyl-N-nitrosourea and H. pylori. Various concentrations of GME (0, 100, 500, and 1,000 ppm) were then fed to the mice for 38 weeks, after which the tumor tissues were examined for histopathology, mucin histochemistry and ${\beta}$-catenin. The incidence of gastric tumors was significantly lower in the highest dose GME-treated mice (46.7%) than control mice (85.7%) (p < 0.05). The multiplicity and size of tumors were also significantly reduced by GME feeding in a dose-dependent manner (p < 0.01). Furthermore, GME suppressed the H. pylori-associated chronic inflammation measured by histologic grading of H. pylori density, chronic gastritis, glandular atrophy and intestinal metaplasia in non-tumorous gastric mucosae. Our data suggest that GME suppresses gastric tumorigenesis via suppression of H. pylori-associated chronic inflammation.

• Korean Journal of Veterinary Research
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• v.52 no.2
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• pp.115-124
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• 2012

Colorectal cancer (CRC) is one of the leading causes of cancer death in western countries or in the developed countries. Zinc intake has been associated with decreased risk of CRC. We investigated the effect of zinc on the formation of colonic aberrant crypt foci (ACF) induced by azoxymethane followed by dextran sodium sulfate in mice. Five-week old ICR mice were fed with the different zinc levels (0.01, 0.1, 1 ppm) for 12 weeks. The numbers of ACF were measured in the colonic mucosa. The ACF number of HZn group was significantly low compared with LZn group or MZn group. Cytosolic superoxide dismutase activity was the highest in HZn group, while thiobarbituric acid reactive substance level for lipid peroxidation was the highest in LZn group. There was no difference in number of PCNA-positive proliferative cells among the groups. TUNEL-positive apoptotic cells were increased in HZn group compared with LZn group. The HZn group exhibited a decrease of ${\beta}$-catenin immunostaining areas compared with the LZn or MZn group. These findings indicate that dietary zinc might exert a protecting effect against colon carcinogenesis by inhibiting the development of ACF in the mice.

• Development and Reproduction
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• v.11 no.3
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• pp.141-153
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• 2007

The Wnt signaling pathway regulates cell proliferation and differentiation during development of multicellular organisms and plays pivotal roles in the maintenance of homeostasis in adult tissues. Therefore misregulation of Wnt signaling could be a pathogenesis of diverse human diseases such as cancers. Recently, the list of diseases that may be linked to the misregulation of Wnt signaling has exploded and more people are getting interested in the way of controlling Wnt signaling. There are a lot of review papers, however, since most of them have focused on specific issues for experts in Wnt signaling it may be difficult for new comers to understand the overall background and current status of Wnt signaling. In this review, we present data and interpretations for the overall processes of Wnt signal transduction to understand the past and current status of Wnt signaling.

• Journal of Embryo Transfer
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• v.25 no.4
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• pp.281-286
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• 2010

This study was to evaluate the protein profile of seminal plasma using 2-DE in Hanwoo. Seminal plasma was harvested from five mature Hanwoo, and seminal plasma protein was extracted by M-PER Mammalian Protein Extraction Reagent. Proteins were refined by clean-up kit and quantified by Bradford method until total protein was $300\;{\mu}l$. Immobilized pH gradient (IPG) strip was used 18 cm and 3~11 NL. SDS-PAGE was used 12% acrylamide gel. Each gels were visualized by comassie brilliant blue and silver staining. These spots were analyzed by MALDI-TOF MS and searched on NCBInr. The result, 20 proteins of 36 protein spots were searched through peptide sequencing on the NCBInr. 8 proteins profiled by 2-DE were proved through previous bovine studies and the name of each protein was albumin, nucleobindin, clusterin, TIMP-2, spermadhesin Z13, spermadhesin-1 and BSP proteins (BSP 30 kDa and BSP A1/A2). 12 new proteins were ATP synthase, protein MAK16 homolog, Transmembrane protein 214, E3 ubiquitin-protein ligase BRE1A, dual serine/threonine and tyrosine protein kinase, tissue factor pathway inhibitor 2, alpha-actinin-4, RUN domain-containing protein 3B, catenin alpha-1, protein-glutamine gamma-glutamyltransferase 2, plakophilin-1 and inter-alpha-trypsin inhibitor heavy chain H1 has not been previously described in the bovine seminal plasma study. These proteins may be contribute to define the type of proteins affecting fertility of male and improve the fertilizing ability of semen in Hanwoo.