Biomedical subjects

Sung-Hoon Kim

Publications and source records attributed to Sung-Hoon Kim.

At least 55 records · Page 3Linked to original sources

PubMed2004

Ras/MAP kinase pathways are involved in Ras specific apoptosis induced by sodium butyrate.

Histone deacetylase inhibitors such as TSA, SAHA, and NaBu etc. are prospective cancer therapeutics of growing interest. Here, we demonstrated that oncogenic ras-transformed rat liver epithelial (WB-ras) cells were specifically undergone apoptosis by 48 h treatment of NaBu. During this, inhibition of ras proteins, especially farnesylated form of ras, and down-regulation of ERK1/2 were observed, which suggest ras/raf/MEK/ERK down-regulation, while p38 MAP kinase was maintained up-regulated. In addition, up-regulation of pro-apoptotic proteins such as p53 and p21CIP1/WAF1, and down-regulation of cell cycle regulator/anti-apoptotic proteins such as cdk2, -4 and phosphorylated Akt were observed concurrently with an increase in apoptotic cell portion. A phosphatase inhibitor, sodium orthovanadate (SOV), efficiently blocked apoptosis and restored responsible proteins for each phenomenon including ERK1/2 while SB203580, a specific p38 MAP kinase inhibitor, showed minor effect on them. Thus, ras/ERK signaling pathway can be considered in chemotherapeutic strategies of NaBu regardless of its inhibitory action on histone deacetylase.

Animals↗

PubMed2004

Roles of p38 and c-jun in the differentiation, proliferation and immortalization of normal human endometrial cells.

BACKGROUND: It has been reported that p38 and c-jun operate as mediators of cell proliferation and differentiation. Therefore, by studying the roles of c-jun and p38 in the proliferation and differentiation of normal human endometrial cells, we can better understand the mechanism of these processes in endometrial cells. METHODS: Separation of glandular and stromal components was based on a modification of the work of Satyaswaroop et al. To confirm the purification of the endometrial cells and the expression of the transfected SV40 large T antigen, immunocytochemical analysis and western blot analysis were performed. RESULTS: There were polygonal shapes in the stromal cells in the early passage 1-2, while the aged endometrial stromal cells were spindle shaped. To investigate passage-dependent molecular events in endometrial cells, the c-jun and pp38 levels were examined. Both c-jun and pp38 were significantly reduced with cellular aging and passages. To understand the role of c-jun, endometrial stromal cells were treated with SP600125 which is a specific inhibitor of c-jun. SP600125 induced morphological changes of young endometrial stromal cells with polygonal shape; the young cells appeared as aged endometrial cells with spindle shape. In addition, an immortalized endometrial cell line was established and shown to express activated c-jun, similiar to normal endometrial cells. CONCLUSIONS: These results suggest that the modulation of p38 and c-jun may play an important role in the differentiation and proliferation of human endometrial cells.

Antigens, Polyomavirus Transforming↗

PubMed2004

Roles of p38 and JNK mitogen-activated protein kinase pathways during cantharidin-induced apoptosis in U937 cells.

Cantharidin is an active compound from blister beetles traditionally used for the treatment of cancer. It is known to exert its antitumor activity by inducing apoptosis in cancer cells. However, its signaling pathway still remains unclear. Therefore, we investigated the roles of the mitogen-activated protein kinases (MAPKs) and the tumor suppressor gene, p53, during cantharidin-induced apoptosis in U937 human leukemic cells. Cantharidin effectively activated ERK-1/2, p38 and JNK in U937 cells in a time- and dose-dependent manner. Cantharidin also exhibited a strong cytotoxicity and induced apoptosis in U937 cells. For the evaluation of the role of MAPKs, PD98059, SB202190 and SP600125 were used as MAPK inhibitors for ERK-1/2, p38 and JNK. PD98059 did not affect cantharidin-induced cytotoxicity and apoptosis, whereas SB202190 and SP600125 significantly interfered with cytotoxic and apoptotic activities induced by cantharidin. Cantharidin alone induced the apoptosis by phosphorylation of p53, up-regulation of downstream target genes, MDM2 and p21 and also cleaved caspase-3, whereas SB202190 and SP600125 caused the down-regulation of p53, MDM-2, p21 and cleaved caspase-3 after a co-treatment with cantharidin. Similarly, SB202190 and SP600125 significantly disturbed the caspase-3 activity after a co-treatment with cantharidin by colorimetric assay. Taken together, these results suggest that cantharidin can induce apoptosis by activation of p38 and JNK MAP kinase pathways associated with p53 and caspase-3.

Apoptosis↗

PubMed2004

Modulations of the Bcl-2/Bax family were involved in the chemopreventive effects of licorice root (Glycyrrhiza uralensis Fisch) in MCF-7 human breast cancer cell.

Recently, cancer chemoprevention with strategies using foods and medicinal herbs has been regarded as one of the most visible fields for cancer control. Genistein in soy, American ginseng, and resveratrol are well-known to have antiproliferative properties in human breast cancer. Licorice root is a botanical, a shrub native to southern Europe and Asia, which primarily has desirable qualities in sweetening and herbal medicine. In this study, licorice (Glycyrrhiza uralensis Fisch) root also inhibits cell proliferation in human breast cancer cell. The cell proliferation study demonstrated that licorice root reduced the proliferation of MCF-7 cells in a dose- and time-dependent manner. The extracts were fractionated in CHCl(3), EtOAc, C(6)H(14), and CH(3)OH-H(2)O (70:30), and these extracts of licorice root (50 microg/mL) induced DNA fragmentation demonstrated by Hoechst 33258 staining. Apoptosis also determined the sub-G1 accumulation by flow cytometry analysis. These results were consistent with specific cleavage of PARP and antiapoptotic protein Bcl-2 and up-regulation of proapoptotic protein Bax demonstrated by Western blotting. Our findings suggest that licorice root may have chemopreventive effects against human breast cancer through the modulation of the expression of the Bcl-2/Bax family of apoptotic regulatory factors.

Anticarcinogenic Agents↗

PubMed2004

Heyneanol A induces apoptosis via cytochrome c release and caspase activation in human leukemic U937 cells.

Heyneanol A, a tetramer of resveratrol, is isolated from the roots of Vitis amurensis by cytotoxicity based fractionation. In this study, the mechanism of apoptosis by heyneanol A was evaluated in human leukemic U937 cells. Heyneanol A (IC(50) = 6.6 microM at 24 h) exhibited stronger cytotoxic effect than resveratrol (IC(50) = 100 microM at 24 h) by 15-fold on human leukemic U937 cells by XTT assay. Apoptotic bodies were observed in U937 cells treated with 6 microM of heyneanol A by TUNEL assay. Heyneanol A effectively increased the portion of sub-G(1) DNA content in a time- and concentration-dependent manner by flow cytometric analysis. Heyneanol A also induced cytochrome c release from mitochondria into the cytosol and subsequent caspase activation involving caspase 9 and 3 to cleave PARP. However, it did not affect the expressions of Bax and Bcl-2 by western blotting. It was confirmed that the activation of caspase 8, 9 and 3 and the cleavage of PARP by heyneanol A were completely blocked by adding Z-VAD-FMK, a caspase inhibitor. These findings suggest that heyneanol A has anti-tumor activity, which may be mediated by apoptosis caused by cytochrome c release and caspase activation in human leukemic U937 cells.

Antineoplastic Agents↗

PubMed2004

Acetylcholinesterase inhibitors from the aerial parts of Corydalis speciosa.

In a bioassay-guided search for acetylcholinesterase inhibitors from Korean natural resources, four isoquinoline alkaloids, corynoxidine (1), protopine (2), palmatine (3), and berberine (4) have been isolated from the methanolic extract of the aerial parts of Corydalis speciosa. Structures of these compounds were elucidated on the basis of spectroscopic techniques. These compounds inhibited acetylcholinesterase activity in a dose-dependent manner, and the IC50 values of compounds 1-4 were 89.0, 16.1, 5.8, and 3.3 microM, respectively.

Acetylcholinesterase↗

PubMed2004

Phytochemical constituents from Diodia teres.

All ten compounds were isolated from the methanolic extract of the whole plants of Diodia teres through repeated silica gel and Sephadex LH-20 column chromatography. Their chemical structures were elucidated as three iridoid glycosides, asperuloside, geniposidic acid and asperulosidic acid, a coumarin glycoside, scopolin, and six flavonoids, rutin, kaempferol-3-O-rutinoside, quercitrin, astragalin, isoquercitrin and quercetin by spectroscopic analysis.

Chemistry, Pharmaceutical↗

PubMed2004

Patterns of treatment failure following radiotherapy with combination chemotherapy for patients with high-risk stage IIB cervical carcinoma.

BACKGROUND: To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy. METHODS: A retrospective analysis of 349 patients with stage IIB cervical carcinoma with high-risk factors (lesion size >/= 4 cm, lymph node metastasis, high-risk cell type) treated by radiotherapy and cisplatin-based chemotherapy was performed. Sites of treatment failure were categorized as pelvic, pelvic plus distant metastases, and distant metastases alone. Pelvic failure included local and pelvic nodal failures. RESULTS: Of the 349 patients, treatment failure occurred in 79 patients (22.6%). Forty-six (13.2%) had persistent disease and 33 (9.5%) had recurrent disease. Among these 79 patients, overall pelvic failure was observed in 67%, of whom 72% had local failure; 19%, pelvic nodal failure; and 9%, local with pelvic nodal failure. Incidences of distant metastases alone and pelvic with distant metastases were 24% and 9%. In the 26 patients with distant metastases either alone or combined with pelvic failure, the most frequent metastatic region was the paraaortic lymph node (50%). The distant metastasis rate was 6.5% (19/289) in the pelvic tumor control group and 11.6% (7/60) in the pelvic failure group. Pelvic failure was the most frequent failure in the group with tumor size of 4 cm or more, whereas, for the positive-lymph-node group, distant metastasis was most frequent and metastases to paraaortic lymph nodes were common. The incidences of pelvic failure alone and distant metastases were similar in the high-risk cell-type group, and the distant metastasis regions were mostly paraaortic lymph nodes. CONCLUSION: Although systemic chemotherapy was administered concurrently with radiotherapy, the incidence of pelvic failure was highest, followed by paraaortic lymph node metastases, in patients with stage IIB cervical carcinoma with high-risk factors, following radiotherapy with combination chemotherapy. To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy.

Adult↗

PubMed2004

Methylene chloride fraction of Scutellaria barbata induces apoptosis in human U937 leukemia cells via the mitochondrial signaling pathway.

BACKGROUND: Scutellaria barbata D.Don has been applied to treat cancers, inflammation and urinary disease. However, its antitumor mechanism still remains unclear. METHODS: With methylene chloride fraction of Herba Scutellariae barbatae (MCSB), apoptosis-related experiments were carried out on human U937 leukemia cells by (a) 2,3-bis[2-4-nitro-5-sulphophenyl]2H-tetrazolium-5-carboxanilide (XTT) assay for cytotoxicity; (b) terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assay for morphological changes; (c) cell cycle analysis; (d) Western blot analysis of poly(ADP-ribose) polymerase (PARP), caspase-8, caspase-9, caspase-3 and Bax, Bcl-2 and cytochrome c expressions for apoptosis signaling pathway. RESULTS: MCSB inhibited the proliferation of human U937 leukemia cells in a dose-dependent manner (IC50 = approximately 10 microg/ml). MCSB dose-dependently increased the sub-G1 DNA contents by cell cycle analysis. DNA fragments indicating induction of apoptosis were observed in MCSB-treated U937 cells by TUNEL assay. Caspase-9 and caspase-3 were activated while caspase-8 was intact by MCSB. Similarly, MCSB effectively cleaved PARP, increased the ratio of Bax/Bcl-2 and released the cytochrome c from mitochondria during apoptosis in U937 cells. CONCLUSIONS: Our results suggest that MCSB can induce apoptosis via the mitochondria-mediated signaling pathway.

Apoptosis↗

PubMed2004

Methanol extract of Dioscoreae Rhizoma inhibits pro-inflammatory cytokines and mediators in the synoviocytes of rheumatoid arthritis.

Dioscoreae Rhizoma (MDR), the root of Dioscorea tokoro MAKINO, has been used for the treatment of arthritis, muscular pain and urinary diseases in oriental medicine. The present work evaluates a methanol extract of Dioscoreae Rhizoma (MDR). MDR did not show any cytotoxic effect on mouse lung fibroblast cells (mLFCs) or human fibroblast-like synovial cells (hFLSCs). However, it significantly reduced the proliferation of hFLSCs stimulated by interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). MDR significantly inhibited the production of TNF-alpha and IL-1beta as well as down-regulating the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in IL-1beta- and TNF-alpha-stimulated hFLSCs. MDR also effectively reduced the level of reactive oxygen species (ROS) in these cells. Taken together, these findings provide evidence that MDR may be a candidate for the treatment of rheumatoid arthritis (RA).

Animals↗

PubMed2004

Effect of Powerdental on caries-inducing properties of Streptococcus mutans and TNF-alpha secretion from HMC-1 cells.

We studied the inhibitory effect of Powerdental on the growth and acid production of Streptococcus mutans as well as secretion of pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). The growth of Streptococcus mutans was reduced by the presence of the Powerdental (1 mg/ml) and NaCl (1 mg/ml) significantly, and the positive control group (1% NaF) also exhibited a significant antibacterial activity. The decrease of pH was significantly inhibited in the presence of Powerdental (1 mg/ml) compared to the control group. The decrease in pH was also inhibited in the presence of positive control (1% NaF), but the bamboo salt alone did not show inhibitory activity. We also found that Powerdental (0.01 mg/ml) inhibited significantly the secretion of TNF-alpha with 46.5+/-0.2% from human mast cells. Our results suggest that Powerdental contributes to the prevention or treatment of periodontitis and other oral diseases or inflammatory diseases.

Acids↗

PubMed2004

Anti-metastatic activity of Acanthopanax senticosus extract and its possible immunological mechanism of action.

Antitumor and immunomodulatory activities of an aqueous extract (GF100) of Acanthopanax senticosus were examined. In experimental lung metastasis of colon26-M3.1 carcinoma cells, intravenous (i.v.) administration of GF100 2 days before tumor inoculation significantly inhibited lung metastasis in a dose-dependent manner. The i.v. administration of GF100 also exhibited the therapeutic effect on tumor metastasis of colon26-M3.1 cells, when it was injected 1 day after tumor inoculation. In an in vitro cytotoxicity analysis, GF100 at the concentration up to 1000 microg/ml did not affect the growth of colon26-M3.1 cells. In contrast, GF100 enhanced the responsiveness to a mitogen, concanavalin A (ConA), of splenocytes in a dose-dependent manner. Peritoneal macrophage stimulated with GF100 produced various cytokines such as IL-1beta, TNF-alpha, IL-12 and IFN-gamma in an in vitro experiment. The macrophages obtained from the mice which were injected with GF100 (500 microg) 3 days before the assay showed significantly higher tumoricidal activity against tumor cells than that of the untreated macrophages. In addition, the i.v. administration of GF100 significantly augmented NK cytotoxicity to Yac-1 cells. The depletion of NK cells by injection of rabbit anti-asialo GM1 serum completely abolished the inhibitory effect of GF100 on lung metastasis of colon26-M3.1 cells. These data suggest that GF100 has antitumor activity to inhibit tumor metastasis prophylactically as well as therapeutically, and its antitumor effect is associated with activation of macrophages and NK cells.

Adjuvants, Immunologic↗

PubMed2004

Sacroiliitis in patients with ankylosing spondylitis: association of MR findings with disease activity.

The purpose of this study was to determine whether MR findings can correlate disease activity as measured by laboratory markers in ankylosing spondylitis. MR images in 19 patients with ankylosing spondylitis were retrospectively analyzed for cartilage abnormality, periarticular erosion, synovial enhancement, and bone marrow edema. Each MR finding was correlated with laboratory inflammatory markers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and the sum of ESR + CRP. Synovial enhancement showed a significant correlation with ESR (r=0.58; p<0.01) and increased activity at bone scan (r=0.74; p<0.005), whereas there was no significant correlation with CRP. A significant correlation was found between ESR + CRP and synovial enhancement (r=0.54; p<0.05). Synovial enhancement was more common when ESR + CRP was greater than 30 (p<0.05). In conclusion, synovial enhancement at MR imaging could correlate disease activity as measured by laboratory inflammatory markers in ankylosing spondylitis.

Biomarkers↗

PubMed2004

Association between iris constitution and apolipoprotein e gene polymorphism in hypertensives.

OBJECTIVE: Iridology is a complementary and alternative medicine (CAM) that involves the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris. Iris constitution has a strong familial aggregation and heredity is implicated. Apolipoprotein E (apoE) gene polymorphism is one of the most well-studied genetic markers for vascular diseases, including hypertension. In this study, we investigated the relationship between iris constitution and apoE polymorphism in hypertensives. DESIGN AND SUBJECTS: We classified 87 hypertensives and 79 controls according to iris constitution and determined the apoE genotype of each individual. RESULTS: A significantly higher percentage of individuals with neurogenic constitutions was found in the hypertensive group when compared with the control group (chi(2) = 40.244, p < 0.001). In addition, a neurogenic constitution increased the relative risk for hypertension for subjects with an apo epsilon2 or an epsilon4 allele (chi(2) = 4.086, p = 0.049, odds ratio = 2.633, confidence interval = 1.004-6.905). CONCLUSIONS: Our results imply that a neurogenic iris constitution enhances the relative risk for hypertension in subjects with the apo epsilon2 or epsilon4 allele. Furthermore, we attempted to evaluate the efficacy of iris constitutional medicine and to find an association with hypertension.

Adult↗

PubMed2004

Polymerase chain reaction analysis of eae gene subtypes present in attaching and effacing Escherichia coli isolated from pigs with diarrhea.

In this study the subtype of eae gene was determined by polymerase chain reaction for a total of 59 attaching and effacing Escherichia coli isolated from preweaned (38 isolates) and postweaned (21 isolates) pigs. The eae(beta) gene detected in 19 E. coli from preweaned pigs and 10 E. coli from postweaned pigs was found to be the most common subtype, followed by eae(gamma), eae(epsilon), and eae(zeta) genes. Subtypes were not determined for 7 E. coli isolates. No other subtype of the eae gene was detected in eae+ E. coli evaluated in this study.

Adhesins, Bacterial↗

PubMed2004

Regulatory effect of dosiinpartner on high-fat diet-induced obesity in C57BL/6J mice.

Dosiinpartner (DSP) is a newly developed dietary functional food to help control weight. The aim of this study was to evaluate whether DSP combined with a high-fat (HF) diet could influence body weight, fat accumulation, and plasma glucose levels. Mice were fed for 8 weeks with normal diet, HF diet, and HF+10% or 20% DSP diet. Body weight was recorded at 1 week, and plasma levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and glucose were analyzed at the end of the study. Weight increases in the 10% or 20% DSP group were significantly less than in the HF diet group (p<0.05). Plasma total cholesterol and LDL cholesterol levels decreased by 48.3% and 26.8% in the 10% DSP group and by 42.9% and 34.9% in the 20% DSP group, respectively. However, the HDL cholesterol level was unchanged. Glucose levels also decreased by 80.6% in the 10% DSP group but was almost the same in the HF and 20% DSP groups. Our findings indicate that DSP may be beneficial in the regulation of high-fat diet-induced overweight and other complications such as circulatory disorders and diabetes mellitus.

Animals↗

PubMed2004

Methylene chloride fraction of Spatholobi Caulis induces apoptosis via caspase dependent pathway in U937 cells.

Spatholobi Caulis has been used in Oriental medicine to treat cancer and blood stasis. In this study, the methylene chloride fraction of Spatholobi Caulis (MCSC) was examined to determine if it possesses anti-cancer activity via its apoptosis-inducing activity. MCSC exhibited a strong cytotoxic effect against human monocyte leukemia U937 cells (IC(50)=15.1 microg/ml). A TUNEL assay showed that the MCSC caused a characteristic ladder pattern of discontinuous DNA fragments and apoptotic bodies. Flow cytometric analysis confirmed that MCSC significantly increases the number of apoptotic cells stained by annexin V(+)/PI(-) cells. Western blotting revealed that MCSC activated caspase-3 expression and cleaved poly (ADP-ribose) polymerase (PARP) in a concentration-dependent manner. An enzyme-linked immunosorbent assay (ELISA) demonstrated that MCSC significantly activated the caspase-3 activity compared with the untreated control by. Taken together, these results suggest that MCSC can induce apoptosis in U937cells via the caspase dependent pathway.

Annexin A5↗

PubMed2004

Immune-enhancing effect of the Korean natural medicine WooKiEum.

WooKiEum (WKE) has been used for the purpose of the development of increased immune-system strength in Korea. In the present study, we examined the anti-immobility effect of WKE on the forced swimming test (FST), and then measured blood biochemical parameters related to fatigue: glucose (Glc), blood urea nitrogen (BUN), lactic dehydrogenase (LDH), creatinine, and total protein (TP). WKE (0.1, 1 g/kg) was administered orally to mice for 7 d. After 2 d, the immobility time was decreased in the WKE-administered group. After 7 d, the immobility time was significantly decreased in the WKE-administered group (64.6+/-9.0 s for 0.1 g/kg) in comparison with the control group (101.3+/-32.7 s). In addition, amount of Glc in the blood serum was increased, whereas the contents of BUN, LDH and TP decreased in the WKE-administered group. Next, we investigated the effect of WKE on the production of cytokines in a human T-cell line, MOLT-4 cells and mouse peritoneal macrophages. WKE (1 mg/ml) significantly increased interferon (IFN)-gamma and TNF-alpha production compared with the media control (about 2.2-fold for IFN-gamma, about 1.7-fold for TNF-alpha, p<0.05) after 24 h. WKE increased the protein expression of IFN-gamma in MOLT-4 cells. These results suggest that WKE may be useful in immune function improvement.

Adjuvants, Immunologic↗