• 대한한의학방제학회지
• /
• 제24권4호
• /
• pp.353-365
• /
• 2016

Objectives : We analysed Gyejibongnyeong-hwan's compatibility principle and investigated biological activities by categorizing with molecular level, cellular level, animal level and human level based on Korean study for this formula. Methods : Gyejibongnyeong-hwan's compatibiltity principle was examined by the system of chief, deputy, assistant, and envoy. We looked into studies that presented in Korea from 1956 to 2016 about Gyejibongnyeong-hwan through Korea Institute of Oriental Medicine, Korean medicine information system (OASIS). Then classify into molecular level, cellular level, animal level and human level to analyse. Results : According to the system of chief, deputy, assistant, and envoy, chief herb is Cinnamomi Ramulus, deputy herb is Persicae Semen, assistant herb is Moutan Cortex, Paeoniae Radix, Poria, and envoy herb is Mel. Biological activities can be detected in transcription factors, enzymes, and inflammatory mediators for molecular level. For cellular level, it can be determined in human uterine endometrial cancer cell, human hepatocarcinoma cell, and human platelets. In mouse and rats for animal level, in overian cystoma, menorrhalgia, quality of life improvement in postmenopausal women, and blood stasis with motor vehicle accident for human level, biological activities was caught. Conclusions : From above results, Gyejibongnyeong-hwan is composed in line with the system of chief, deputy, assistan, and envoy. Biological activities are effective to improvement of menorrhalgia, anti-cancer, anti-oxidative, anti-inflammation, improvement of atherosclerosis, analgesic, anti-convulsion, wound healing, and improvement of liver function.

• Journal of Microbiology and Biotechnology
• /
• 제17권9호
• /
• pp.1513-1520
• /
• 2007

[ ${\beta}$ ]-1,3-Glucans enhance immune reactions such as antitumor, antibacterial, antiviral, anticoagulatory, and wound healing activities. ${\beta}$-1,3-Glucans have various functions depending on the molecular weight, degree of branching, conformation, water solubility, and intermolecular association. The molecular weight of the soluble glucan was about 15,000 as determined by a high-performance size exclusion chromatography. From the infrared (IR) and $^{13}C$ NMR analytical data, the purified soluble glucan was found to exclusively consist of ${\beta}$-D-glucopyranose with 1,3 linkage. We tested the immunestimulating activities of the soluble ${\beta}$-1,3-glucan extracted from Agrobacterium sp. R259 KCTC 1019 and confirmed the following activities. IFN-$_{\gamma}$ and each cytokines were induced in the spleens and thymus of mice treated with soluble ${\beta}$-1,3-glucan. Adjuvant effect was observed on antibody production. Nitric oxide was synthesized in monocytic cell lines treated with ${\beta}$-1,3-glucan. The cytotoxic and antitumor effects were observed on various cancer cell lines and ICR mice. These results strongly suggested that this soluble ${\beta}$-1,3-glucan could be a good candidate for an immune-modulating agent.

• 생명과학회지
• /
• 제15권2호
• /
• pp.231-235
• /
• 2005

기질 금속단백분해효소(MMP)는 기저막이나 간질성 조직 등에 있는 세포외기질 성분을 분해하여 상처 치유, 태아의 발생, 종양세포의 침윤과 전이 등을 포함하여 조직이 재구성되는 과정에서 생리학적 및 병리학적인 과정 양쪽 모두에 매우 중요한 역할을 한다. 본 연구에서는 MMP-9 유전자의 발현을 억제하는 물질을 천연물에서 탐색하였고, 탐색된 시료 중에서 높은 역가를 가진 낙우송과의 Metasequoia glyptostroboides가 선택되었다. 여러 가지 flavonoid 성분을 가지고 있는 Metasequoia glyptostroboides를 이용하여 4개의 biflavonoid와 2개의 monoflavonoid 구조의 물질을 분리하였고, 이 flavonoid들은 sciadopitysin, isoginkgetin, bilobetin, 2, 3-dihydrohino-kiflavone, luteolin, apigenin으로 정제하여 구조를 밝히고 zymography, WST-1을 이용한 세포독성시험, northern blot 등의 실험을 통하여 각 화합물의 구조적인 특성과 함께 MMP-9 유전자 발현을 억제하는 효과가 있는 것을 확인하였다.

• Genomics & Informatics
• /
• 제11권4호
• /
• pp.245-253
• /
• 2013

A radioresistant cell line was established by fractionated ionizing radiation (IR) and assessed by a clonogenic assay, flow cytometry, and Western blot analysis, as well as zymography and a wound healing assay. Microarray was performed to profile global expression and to search for differentially expressed genes (DEGs) in response to IR. H460R cells demonstrated increased cell scattering and acidic vesicular organelles compared with parental cells. Concomitantly, H460R cells showed characteristics of increased migration and matrix metalloproteinase activity. In addition, H460R cells were resistant to IR, exhibiting reduced expression levels of ionizing responsive proteins (p-p53 and ${\gamma}$-H2AX); apoptosis-related molecules, such as cleaved poly(ADP ribose) polymerase; and endoplasmic reticulum stress-related molecules, such as glucose-regulated protein (GRP78) and C/EBP-homologous protein compared with parental cells, whereas the expression of anti-apoptotic X-linked inhibitor of apoptosis protein was increased. Among DEGs, syntrophin beta 2 (SNTB2) significantly increased in H460R cells in response to IR. Knockdown of SNTB2 by siRNA was more sensitive than the control after IR exposure in H460, H460R, and H1299 cells. Our study suggests that H460R cells have differential properties, including cell morphology, potential for metastasis, and resistance to IR, compared with parental cells. In addition, SNTB2 may play an important role in radioresistance. H460R cells could be helpful in in vitro systems for elucidating the molecular mechanisms of and discovering drugs to overcome radioresistance in lung cancer therapy.

• 대한치과보존학회:학술대회논문집
• /
• 대한치과보존학회 2003년도 제120회 추계학술대회 제 5차 한ㆍ일 치과보존학회 공동학술대회
• /
• pp.545-545
• /
• 2003

Chitosan is applied as a dressing for oral mucous wound and a tampon following radical treatment of maxillary sinus. Furthermore, it is being investigated as an absorbing membrane for endodontic and periodontic surgeries. A few studies have reported osteoconduction and osteogenesia at the site of chitosan implant in vivo. However, compared with soft tissue healing processes, the mechanisms concerning effects of chitosan for biological mineralization have not yet been resoil In the present study, we studied the gene expression pattern using cDNA microarray and RT-PCR analyses in hard tissue forming osteoblasts cultured with water-soluble and low molecular weight chitooligosaccharide. cDNA microarray analysis revealed that 16 genes were expressed at 〉1.5-fold higher signal ratio levels in the experimental group compared with the control group after 3 days. RT-PCR analysis showed that chitosan oligomer induced an increase in the expression of two genes, CD56 antigen and tissue-type plasminogen activator. Furthermore, the expression of mRNAs for BMP-2 was almost identical in the experimental and control groups after 3 days of culture, but slightly increased after 7 days of culture with chitosan oligomer. These results suggest that a super-low concentration of chitooligosaccharide could modulate the activity of osteoblastic cells through mRNA levels and that the genes concerning cell proliferation and differentiation can be controlled by water-soluble chitosan.

• Journal of Ginseng Research
• /
• 제43권1호
• /
• pp.68-76
• /
• 2019

Background: In colorectal cancer (CRC), 40-60% of patients develop metastasis. The epithelial-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of CRC. The aim of this study was to investigate the effect of Korean Red Ginseng extract (RGE) on colorectal metastasis through inhibition of EMT and the metastatic abilities of CRC cells. Methods: To investigate the effect of RGE on the metastatic phenotypes of CRC cells, CT26 and HT29 cells were evaluated by using an adhesion assay, a wound-healing assay, an invasion assay, zymography, and real-time reverse transcription-polymerase chain reaction. Western-blot analysis was conducted to elucidate the molecular mechanisms of RGE, which showed an inhibitory effect on the transforming growth factor-${\beta}1$ ($TGF-{\beta}1$)-induced EMT in HT29 cells. Additionally, the antimetastatic effect of RGE was evaluated in a mouse model of lung metastasis injected with CT26 cells. Results: RGE decreased the adhesion and migration ability of the CT26 cells and TGF-${\beta}1$-treated HT29 cells. The invasion ability was also reduced by RGE treatment through the inhibition of matrix metalloproteinase-9 expression and activity. Moreover, RGE suppressed the TGF-${\beta}1$-induced EMT via TGF-${\beta}1$/Smad-signaling-mediated Snail/E-cadherin expression in HT29 cells and lung tissue in CT26 tumor-bearing mice. Conclusion: Our results demonstrated that RGE inhibited colorectal lung metastasis through a reduction in metastatic phenotypes, such as migration, invasion, and the EMT of CRC cells.

• BMB Reports
• /
• 제52권9호
• /
• pp.548-553
• /
• 2019

Ets-1 is a prototype of the ETS protein family. Members of the ETS protein family contain a unique ETS domain. Ets-1 is associated with cancer progression and metastasis in many types of cancer. Many studies have shown a link between elevated expression of Ets-1 in cancer biopsies and poor survival. CCR7 is a chemokine that binds to specific ligand CCL21/CCL19. CCR7 expression is associated with tumor metastasis and infiltration into lymph nodes. The objective of this study was to test whether Ets-1 could regulate CCR7 expression and enhance tumor metastasis. Our data showed that CCR7 expression was downregulated in Ets-1-deficient T cells upon T-cell stimulation. Overexpression of Ets-1 increased CCR7 expression in breast cancer cell lines. In contrast, knockdown of Ets-1 reduced CCR7 expression. Ets-1 could directly bind to CCR7 promoter and mediate CCR7 expression in luciferase reporter assays and chromatin immunoprecipitation assays. Transactivation activity of Ets-1 was independent of the Pointed domain of Ets-1. Ets-1 could also enhance $NF-{\kappa}B$ and CBP transactivation of CCR7 promoter. Our results also showed that Ets-1 could modulate cancer cell transmigration by altering CCR7 expression in transwell assay and wound healing assay. Taken together, our data suggest that Ets-1 can enhance CCR7 expression and contribute to tumor cell migration.

• Journal of Gastric Cancer
• /
• 제21권4호
• /
• pp.439-456
• /
• 2021

Purpose: Gastric cancer (GC) has high morbidity and mortality and is a serious threat to public health. The flavonoid compound vitexin is known to exhibit anti-tumor activity. In this study, we explored the therapeutic potential of vitexin in GC and its underlying mechanism. Materials and Methods: The viability, migration, and invasion of GC cells were determined using MTT, scratch wound healing, and transwell assays, respectively. Target molecule expression was determined by western blotting. Tumor growth and liver metastasis were evaluated in vivo using nude mice. Protein expression in the tumor tissues was examined by immunohistochemistry. Results: Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner. Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing HMGB1 expression. Vitexin-mediated inhibition in proliferation, migration, invasion and EMT of GC cells were counteracted by hyper-activation of PI3K/AKT/HIF-1α pathway or HMGB1 overexpression. Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression. Conclusions: Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway. Thus, vitexin may serve as a promising therapeutic agent for the treatment of GC.

• 한국발생생물학회지:발생과생식
• /
• 제25권2호
• /
• pp.93-104
• /
• 2021

Cutaneous melanoma is a fatal disease for patients with distant metastasis. Metformin is the most widely used anti-diabetic drug, and proved to suppress cell proliferation and metastasis in diverse cancers including melanoma. We previously reported that MEK inhibitor trametinib increases the expression of epithelial-mesenchymal transition (EMT) regulators and melanoma cell motility, which are suppressed by addition of metformin in A375 melanoma cells. To confirm our findings further, we first evaluated the effect of metformin in combination with another MEK inhibitor binimetinib on cell viability in G361 melanoma cells. We then investigated whether binimetinib affects the expression of EMT regulators and cell motility. We finally monitored the effect of metformin on binimetinib-induced cell migration. Cell viability assay showed that combination index (CI) value at ED₅₀ is 0.80, suggesting synergy for the combination of metformin with binimetinib. Our results also revealed that binimetinib increased the expression of EMT regulators such as integrin αV, fibronectin and slug, which correlate well with the enhanced cell migration in wound healing assay. Metformin, on the contrary, suppressed the expression of sparc, integrin αV, fibronectin and N-cadherin with the reduced cell motility. The combination treatment showed that metformin counteracts the binimetinib-induced increase of cell motility. Overall, these results suggest that metformin with binimetinib might be useful as a potential therapeutic adjuvant against cell survival and metastatic activity in melanoma patients.

• 대한본초학회지
• /
• 제32권3호
• /
• pp.55-61
• /
• 2017

Objectives : The aim of this research was to determine the diverse effects of Lithospermi Radix Water Extract (LR) on human keratinocyte HaCaT cells, and to examine whether those effects could be applied to the human skin. Methods : We examined effect of LR on the cell viability of using the MTS assay in human keratinocyte HaCaT cells. The antioxidation effect of LR was analyzed relative to the well-known antioxidant resveratrol, using an ABTS assay. Quantitative RT-PCR analysis revealed that, in HaCaT cells, LR influenced the mRNA expression of tight-junction genes associated with skin moisturization. Furthermore, a wound-healing assay demonstrated altered cell migration in LR-treated HaCaT cells. Result : The cytotoxicity was confirmed to be higher in LR at a concentration of $800{\mu}g/m{\ell}$ using the MTS assay in HaCaT cells. In comparison to $100{\mu}M$ resveratrol, $1,600{\mu}g/m{\ell}$ LR showed either a similar or superior antioxidation effect. LR treatment in HaCaT cells reduced the mRNA expression levels of claudin 3, claudin 4, claudin 6, claudin 8, and ZO-2 to less than 0.80-fold, whereas JAM-A and Tricellulin mRNA expression level increased more than 1.33-fold. In addition, HaCaT cells migration was decreased to 83.9% by LR treatment. Conclusions : LR of antioxidation activity will have an anti-aging effect on the skin by reducing oxidative stress. Further studies are required to address the implications for human skin, given LR's effects of altering mRNA expression of tight junction-related gene and decreasing cell migration of HaCaT cells.