• Tuberculosis and Respiratory Diseases
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• v.48 no.1
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• pp.24-32
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• 2000

Purpose: Microsatellite instability(MSI) is frequently used as an indicator of microsatellite mutator phenotype(MMP) tumors. MSI has been observed in a percentage of non-small cell lung cancer(NSCLC). However, its role in tumorigenesis of NSCLC remains unknown. The frequency and pattern of MSI in NSCLC were evaluated and clinical parameters of MSI-positive tumors with those of MSS(microsatellite stable) tumors were compared. Materials and Methods: Twenty surgically resected NSCLCs were analyzed for 15 microsatellite markers located at chromosomes 3p and 9p. The peripheral blood lymphocytes of patients were used as the source of the normal DNA. Results: 1) Of 20 cases, 8(40%) demonstrated MSI. 2) Instability was observed more frequently in tri- and tetra-nucleotide repeats than in dinucleotide repeats. In all cases, instability appeared as a shift of individual allelic bands. 3) LDH was observed in 10(50%) of 20 tumors analyzed. 4) Of 20 cases, MSI-H tumor(showing MSI in the majority of markers) was absent. There were 5 MSI-L tumors(showing MSI in a greater than 10% of markers). 5) No significant difference was observed between MSI-L tumors and MSI-negative tumors in terms of clinicopathologic features such as pack-year history of smoking, histologic subtype, and(delete) stage of disease. There was also no significant difference in the incidence of LDH in relation to the status of MSI. Conclusion: These data strongly suggest that MSI plays different roles in lung and colon cancer. MMP pathway appears to be far less important in the tumorigenesis of NSCLC, caused mainly by cigarette smoke, with little familial tendency.

• BMB Reports
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• v.38 no.6
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• pp.709-716
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• 2005

Apoptosis and necrosis are distinguished by modality primarily. Here we show an apoptosis occurred instantly, induced by $300\;{\mu}M$ W-7 ((N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride), inhibitor of calmodulin), which demonstrated necrotic modality. As early as 30 min after W-7 addition, apoptotic (sub-diploid) peak could be detected by fluorescence-activated cell sorter (FACS), “DNA ladders” began to emerge also at this time point, activity of caspase-3 elevated obviously within this period. Absence of mitochondrial membrane potential (MMP) reduction and cytochrome c, AIF (apoptosis inducing factor) release, verified that this rapid apoptosis did not proceed through mitochondria pathway. Activation of caspase-12 and changes of other endoplasmic reticulum (ER) located proteins ascertained that ER pathway mediated this necrosis-like apoptosis. Our findings suggest that it is not credible to judge apoptosis by modality. Elucidation of ER pathway is helpful to comprehend the pathology of diseases associated with ER stress, and may offer a new approach to the therapy of cancer and neurodegenerative diseases.

• Korean Journal of Pharmacognosy
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• v.46 no.4
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• pp.295-302
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• 2015

Cynanchi wilfordii Radix roots have been utilized as traditional medicine for variety of diseases including diabetes mellitus, aging progression and scavenging free radicals, enhancing immunity, reducing high serum cholesterol, and anti-tumor activity. However, the mechanisms underlying this effect remain poorly understood. The principal objective of this study was to determine the effect of cynandione A on osteoclast cells. Thus, we was isolated cynandione A from Cynanchi wilfordii Radix roots and evaluated the effect of cynandione A on receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. We found that cynandione A significantly inhibited osteoclast differentiation stimulated-RANKL in RAW 264.7 cells. Cynandione A conspicuously inhibited the mRNA and protein expression of matrix metallopeptidase 9 (MMP-9), tartrate-resistant acid phosphatase (TRAP) in cynandione A treated with RANKL. Taken together, our results demonstrated that Cynanchi Wilfordii Radix may be useful treatment option of bone-related disease such as osteoporosis leads to fracture of bone and rheumatoid arthritis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.12
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• pp.1708-1716
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• 2016

The Akt/mammalian target of the rapamycin (mTOR) pathway is activated in the majority of human cancers. Activation of the Akt/mTOR pathway confers resistance to many types of cancer therapy. In this study, we evaluated the apoptotic effect of ethanol extract of Artemisia annua L. through down-regulation of Akt signal pathways and the mitochondrial pathway in hepato-carcinoma cells (HepG2). A. annua extract is known as a medicinal herb that is effective against cancer. We evaluated anti-proliferative activity by MTT-based viability assay and apoptotic effect by Annexin-V/PI staining, mitochondrial membrane potential (MMP), and caspase-3/7 activity as determined by flow cytometry. A. annua treatment led to loss of MMP, resulting in cytochrome c-inducible activation of caspase-3/7. Treatment with A. annua extract reduced activities of Akt/mTOR/anti-apoptotic proteins (such as Bcl-2 and $Bcl-X_L$), leading to increased activation of tumor suppressor p53 and pro-apoptotic proteins (such as Bax and Bak). We applied LY294002 (inhibitor of Akt) and rapamycin (inhibitor of mTOR) to determine the relationship between signal transduction of proteins associated with apoptosis. LY294002 and rapamycin significantly reduced cell viability and increased apoptosis. These results indicate that Bcl-2 and caspase-3 are key regulators in A. annua extract-induced apoptosis in HepG2 cells and are controlled through the Akt/mTOR signaling pathway.

• Journal of Life Science
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• v.26 no.7
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• pp.789-795
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• 2016

A lymph node (LN) is one of the secondary lymphoid organs. An LN consists of a complicated 3 dimensional frame structure and several stromal cells. Fibroblastic reticular cells (FRC) are distributed in the T zone for interaction with T cells. FRC secrete homing chemokines such as CCL19 and CCL21. Moreover, FRC play a pivotal role in the production of extracellular matrix (ECM) into LN for ECM reorganization against pathogen infections. However, not much is known about the involvement of the immune reaction of FRC. The present report is for the characterization of FRC on immune response. For this, FRC were positioned in several infected situations such as co-culture with macrophage, lipopolysaccharide (LPS), and TNFα stimulation. When a co-culture between FRC and macrophage was performed, a morphological change in FRC was observed, and empty space between FRCs was created by this change. The soluble ICAM-1 protein level was up-regulated by co-culturing with Raw264.7 and the treatment of the ROCK inhibitor Y27632. The activity of matrix metalloproteinase (MMP) was up-regulated by LPS onto FRC. Furthermore, the inflammatory cytokine TNFα regulated the expression of ECM in FRC by a gene chip assay. Collectively, it suggests that FRC are involved in immune reactions.

• Molecules and Cells
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• v.46 no.4
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• pp.245-255
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• 2023

This study aimed to exploring the pathophysiological mechanism of 7α,25-dihydroxycholesterol (7α,25-DHC) in osteoarthritis (OA) pathogenesis. 7α,25-DHC accelerated the proteoglycan loss in ex vivo organ-cultured articular cartilage explant. It was mediated by the decreasing extracellular matrix major components, including aggrecan and type II collagen, and the increasing expression and activation of degenerative enzymes, including matrix metalloproteinase (MMP)-3 and -13, in chondrocytes cultured with 7α,25-DHC. Furthermore, 7α,25-DHC promoted caspase-dependent chondrocyte death via extrinsic and intrinsic pathways of apoptosis. Moreover, 7α,25-DHC upregulated the expression of inflammatory factors, including inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E₂, via the production of reactive oxygen species via increase of oxidative stress in chondrocytes. In addition, 7α,25-DHC upregulated the expression of autophagy biomarkers, including beclin-1 and microtubule-associated protein 1A/1B-light chain 3 via the modulation of p53-Akt-mTOR axis in chondrocytes. The expression of CYP7B1, caspase-3, and beclin-1 was elevated in the degenerative articular cartilage of mouse knee joint with OA. Taken together, our findings suggest that 7α,25-DHC is a pathophysiological risk factor of OA pathogenesis that is mediated a chondrocyte death via oxiapoptophagy, which is a mixed mode of apoptosis, oxidative stress, and autophagy.

• International Journal of Oral Biology
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• v.35 no.4
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• pp.145-151
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• 2010

Periodontitis is an inflammatory disorder of the periodontium and is characterized by destruction of the tooth supporting tissues, mediated by the upregulation of synthesis and release of a variety of pro-inflammatory factors. Inflammatory cytokines and prostaglandins upregulate RANKL and its subsequent binding to RANK stimulates osteoclast formation, resorption activity, and survival. In our present study, we investigated the effects of HP08-0111, composed of Coptis japonica (Thunb.) Makino, vitamin C and vitamin E, upon inflammatory responses, osteoclastogenesis and alveolar bone loss. HP08-0111 decreased the expression of IL-1$\beta$ and COX2 on LPS-induced RAW 264.7 cells and inhibited osteoclast-specific genes such as c-Fos, MMP-9, and TRAP. HP08-0111 also exhibited protective effects against alveolar bone loss in rats with ligature-induced periodontitis. Our results suggest that HP08-0111 is potentially an important therapeutic tool for the treatment of disorders associated with bone loss such as periodontitis.

• The Journal of Korean Obstetrics and Gynecology
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• v.25 no.2
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• pp.23-42
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• 2012

Objectives: This study was performed to evaluate the effect of Samkieumgamibang (SKG) on osteoporosis. Methods: The osteoclastogenesis and gene expression were determined in RANKL-stimulated RAW 264.7 cell. And, osteoblastogenesis was also determined in rat calvarial cell. Results: SKG decreased the number of TRAP positive cell in osteoclast. It also decreased the expression of Cathepsin K, MMP-9, TRAP, c-fos, NAFTc1 and JNK1 in osteoclast. SKG increased the expression of iNOS in RANKL-stimulated in osteoclast. Otherwise, SKG inhibited TRAP activity in osteoclast. SKG increased cell proliferation, ALP activity, bone martix protein, collagen and nodule in osteoblast. Conclusions: It is concluded that SKG might decrease the bone resorption resulted from decrease of osteoclast differentiation and it's related gene expression. And, SKG might increase the bone formation resulted from increase of osteoblast function.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.192.2-192.2
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• 2003

Apigenin-7-O-${\beta}$-D-glucoside, chrysoeriol, and luteolin were isolated from the aqueous ethanolic extract of Zostera marina L. leaves as the scavengers of reactive oxygen species (ROS) with the SC$\_$50/ values of 0.18 mM, 0.68 mM, and 0.18 mM against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 0.04 mM, 0.03 mM, and 0.01 mM against superoxide radicals in the xanthine/xanthine oxidase system, respectively. The luteolin suppressed the expression of matrix metalloproteinase-1 (MMP-1) up to 44% at 4.0 ${\mu}$M. (omitted)

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.3
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• pp.59-67
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• 2023

Purpose : Epithelial-to-mesenchymal transition (EMT) is recognized as an important cellular response in metastatic proceduresand characterized by loss of cellular polarity as well as gain of mesenchymal features, which enables migration and invasion. Hepatocellular carcinoma (HCC) is one of the most common primary carcinomas in the liver and exhibits a poor prognosis due to frequent extrahepatic metastasis. Taraxacum officinale has been used for a long time in oriental medicine because of its various pharmacological activitiessuch as anti-rheumatic, anti-inflammatory, antioxidative, and anticarcinogenic activities. In this study, the anti-metastatic activity of T. officinale water extract (TOWE) and ethanol extract (TOEE) was investigated through the regulation of EMT in the Huh7 cells. Methods : The effects of TOWE and TOEE on migratory and invasive activities were investigated by wound healing and in vitro invasion assays. Western blot analysis was also applied to analyze protein expression levels associated with EMT and their upstream transcription factors in Huh7 cells. Results : TOWE and TOEE treatment potently inhibited migration and invasion of Huh7 cells compared to the untreated group. Both extracts treatment inhibited protein expression levels of N-cadherin, matrix metalloproteinase (MMP)-9, and vimentin while E-cadherin was significantly accelerated. In addition, the activated status of transcription factors, Snail, nuclear factor (NF)-κ B, and zinc finger E-box binding homeobox (ZEB)1 was also inhibited with statistical significance. In comparison to both extracts, TOEE more potently attenuated migration, invasion, and EMT markers as well as their transcription factors in Huh7 cells than TOWE, which means that TOEE might possess more functional phytochemicals than TOWE. Conclusion : Consequently, TOWE and TOEEattenuated metastatic activity of hepatocellular carcinoma through the regulation of EMT markers and their transcription factors in Huh7 cells, which means that T. officinale might be a promising strategy for a chemopreventive agent against HCC metastasis.