• Journal of Applied Biological Chemistry
• /
• v.52 no.4
• /
• pp.180-186
• /
• 2009

Whole plants of Vitex rotundifolia were extracted for 2 days with methylene chloride ($CH_2Cl_2$) followed by extraction of the residue for an additional 2 days. The same procedure was also applied using methanol (MeOH). The two crude extracts were combined and partitioned between $CH_2Cl_2$ and $H_2O$. The organic layer was further partitioned between n-hexane and 85% aq. MeOH, and the aqueous layer was also further fractionated with n-BuOH and $H_2O$, successively. From the 85% aq. MeOH fraction, one compound was isolated through the repeated HPLC. According to the results of physicochemical data including NMR and MS, the chemical structure of the compound was determined as artemetin (1). The antiproliferative effects of the crude extracts, fractions, and compound against HT1080, AGS, MCF-7 and HT-29 human cancer cells were compared with the control by using MTT assay. In the comparative analysis, the 85% aq. MeOH fraction exhibited the strongest antiproliferative effects on human cancer cell lines in a dose-dependent manner (p<0.05). In addition, exposure of compound 1 isolated from 85% aq. MeOH fraction led to strong antiproliferative effect in HT1080 cancer cell lines. These results suggest that the extracts and compound isolated from V. rotundifolia may be used as potential chemopreventive and chemotherapeutic agents.

• Microbiology and Biotechnology Letters
• /
• v.45 no.2
• /
• pp.101-109
• /
• 2017

This study investigated the effect of the dichloromethane fraction form Katsuwonus pelamis heart on anti-inflammatory responses in lipopolysaccharide-stimulated RAW 264.7 cells and mouse models. Ethanol extract was partitioned with dichloromethane, ethyl acetate, butanol, and water. Among the fractions, the dichloromethane fraction showed a significant decrease in nitric oxide (NO) and pro-inflammatory cytokines [interleukin (IL)-6, $IL-1{\beta}$, and tumor necrosis $factor-{\alpha}$] production compared to ethanol extract. The dichloromethane fraction attenuated the expression of inducible nitric oxide synthase and nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) p65 proteins in a dose-dependent manner. In addition, the expression of phosphorylation of mitogen-activated protein kinases (MAPKs) was also inhibited by the dichloromethane fraction. Moreover, the administration of 10, 50, and 250 mg/kg body weight-dose dependently inhibited the formation of edema by croton-oil and the application of dichloromethane (2 mg/ear) significantly reduced epidermal and dermal thickness and the infiltrated mast cell numbers. Therefore, the dichloromethane fraction exhibited an anti-inflammation effect by inhibiting $NF-{\kappa}B$ and MAPK signaling activation in macrophages.

• KSBB Journal
• /
• v.23 no.2
• /
• pp.177-182
• /
• 2008

In this study, crude extracts of the halophyte Limonium tetragonum and their solvent fractions were evaluated on anticancer activity in AGS and HT-29 human cancer cells using MTT assay. Each of the crude extracts (MeOH and $CH_2Cl_2$) of Limonium tetragonum showed a significant inhibitory effect on the growth of human cancer cells. The combined crude extracts of MeOH and $CH_2Cl_2$ were partitioned between $CH_2Cl_2$ and water. The organic layer was further partitioned between 85% aq. MeOH and n-hexane, and then the aqueous layer was fractionated with n-BuOH and $H_2O$, successively. Growth inhibition effects of crude extracts and their solvent fractions from Limonium tetragonum increased in a dose-dependent manner. Among them, 85% aq. MeOH, n-hexane and n-BuOH fractions revealed very good inhibition effects on the growth of human cancer cells. These results suggest that we can isolate active compounds from Limonium tetragonum to show much more strong anticancer activity.

• Clinical and Experimental Pediatrics
• /
• v.48 no.2
• /
• pp.186-190
• /
• 2005

Purpose : The purpose of this study was to evaluate the responses and toxicities of risk-adapted chemotherapy in pediatric intracranial germ cell tumors(IC-GCT). Methods : Fourteen patients who were diagnosed as IC-GCT from October 2002 to December 2003 received chemotherapy as an initial treatment modality. The low risk(LR) group was defined as follows : Pure germinoma and normal AFP level. Beta-hCG level 50 mIU/mL or less. The others belonged to the high risk(HR) group. Chemotherapy was composed of cisplatin, cyclophosphamide, etoposide and vincristine. Double doses of cisplatin and cyclophosphamide was used in HR patients. Results : Pathologic confirmation was done in all but one. Median age at diagnosis was 11.6 yr (1.2-18.7 yr), and nine patients belonged to the HR group. Tumor markers were normalized after chemotherapy in all patients whose tumor markers had been elevated. Four LR patients(80 percent) and seven HR patients(77.8 percent) showed complete response(CR) at the end of chemotherapy. An additional two of the three patients with partial response(PR) achieved CR after radiation therapy (RT), and the remaining one relapsed before RT. Four LR and all HR patients experienced infectious episodes that required hospitalization. Four of the nine HR patients(44.4 percent) suffered from tinnitus, three of whom developed sensorineural hearing loss. All but one are surviving, event-free, with a median follow-up of 13.9 mo(8.1-22.3 mo). Conclusion : Risk-adapted cisplatin-based chemotherapy was effective even in HR patients, but regimen modification seems to be necessary to avoid an unacceptably high toxicity rate.

• Journal of Chest Surgery
• /
• v.37 no.8
• /
• pp.691-701
• /
• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• Journal of Life Science
• /
• v.30 no.4
• /
• pp.370-378
• /
• 2020

This study aimed to investigate the hepatoprotective effect of Dendropanax morbifera (D. morbifera) leaf hot-water extract on carbon tetrachloride (CCl₄)-treated HepG2 cells. Treatment with D. morbifera leaf hot-water extract increased the cell viability of CCl₄-treated HepG2 cells without inducing cytotoxicity. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) released by CCl₄-treated cells were 27.6 U/L and 52.4 U/L, respectively, and were significantly higher than those in untreated control cells (10.0 U/L and 15.2 U/L, respectively). Moreover, the level of γ-glutamyl transpeptidase (GGT) was 5.4 times higher, while that of glutathione was 44.0% lower in CCl₄-treated cells than in control cells. However, treatment with D. morbifera leaf hot-water extract resulted in a dose-dependent decrease in the levels of ALT, AST, and GGT, and an increase in the level of glutathione. Moreover, the malondialdehyde (MDA) content in CCl₄-treated HepG2 cells was effectively reduced after treatment with D. morbifera leaf hot-water extract. Additionally, overproduction of intracellular lipids induced by CCl₄ treatment was effectively inhibited by D. morbifera leaf hot-water extract treatment. Furthermore, DCFDA staining showed that overproduction of reactive oxygen species (ROS) induced by CCl₄ treatment was effectively reduced by treatment with D. morbifera leaf hot-water extract. Our results indicate that owing to its beneficial effects, D. morbifera leaf extract has considerable potential as a functional food material for liver protection.

• Journal of Life Science
• /
• v.28 no.5
• /
• pp.524-531
• /
• 2018

The essential oil from Abies koreana E.H. Wilson had been developed, however, its efficacy has not yet been studied especially in terms of skin care research. The aim of this study is to investigate the effects of Abies koreana extracts (AKE) on melanogenesis and wrinkle formation in B16F10 melanoma cells (B16F10) and human dermal fibroblast cell line (HDF). The essential oil was extracted by hydrodistillation method and purified by anhydrous sodium sulfate. At a concentration of $10^{-5}$-fold, viability in these cells had been defined by cytotoxicity assays. Anti-melanogenic effects on B16F10 were evaluated using tyrosinase inhibition assay, and real-time PCR for verifying gene expression of tyrosinase, tyrosinase related protein-1 and -2 (TRP-1 and -2). AKEs reduced about 5-fold of tyrosinase inhibitory activity compared to ${\alpha}$-melanocyte-stimulating hormone (${\alpha}$-MSH)-induced group and about 30% reduction compared to Arbutin induced group. The mRNA levels of three melanin-related factors were increased, separately. To investigate the effects of anti-wrinkle, procollagen type I c peptide synthesis assay (PIP) and Western blot were performed. At AKE-treated group, PIP was up-regulated and the expression of collagen type 1 and matrix metalloproteinase (MMP)-1 were improved. Furthermore, AKE presented anti-wrinkle effects by increasing UVB-inhibited collagen type 1 expression, and reducing UVB-induced MMP-1 production at $60mJ/cm^2$ of UVB radiation. Therefore, Abies koreana extracts has potentials as a safe and an effective skin ingredient for whitening and anti-wrinkle.

• Journal of Life Science
• /
• v.23 no.5
• /
• pp.609-615
• /
• 2013

Glyceollin I has gained attention as a useful therapy for various dermatological diseases. However, the binding property of glyceollin I to the mammalian adenylyl cyclase (hereafter mAC), a critical target enzyme for the down-regulation of skin melanogenesis, has not been fully explored. To clarify the action mechanism between glyceollin I and mAC, we first investigated the molecular docking property of glyceollin I to mAC and compared with that of SQ22,536, a well-known mAC inhibitor, to mAC. Glyceollin I showed superiority by forming three hydrogen bonds with Asp 1018, Trp 1020, and Asn 1025, which exist in the catalytic site of mAC. However, SQ22,536 formed only two hydrogen bonds with Asp 1018 and Asn 1025. Secondly, we confirmed that glyceollin I effectively inhibits the formation of forskolin-induced cAMP and the phosphorylation of PKA from a cell-based assay. Long term treatment with glyceollin I had little effect on the cell viability. The findings of the present study also suggest that glyceollin I may be extended to be used as an effective inhibitor of hyperpigmentation.

• Tuberculosis and Respiratory Diseases
• /
• v.41 no.6
• /
• pp.632-643
• /
• 1994

Background: The objective responses of cisplatin and etoposide (PVP) combination chemotherapy as second-line therapy following CAV was high (40~50%) and, in several reports, PVP yields survival results that are at least as good as those obtained with cyclophosphamide or doxorubicin-based regimens and with less host-related toxicity in chemotherapy-naive patients. We conducted a phase II study to evaluate the effect of a combination of cisplatin and etoposide as a fitst-line therapy in patients with small cell lung cancer. Methods: Sixty-one previously untreated small cell lung cancer patients with measurable lesion (s) received cisplatin(30 $mg/m^2$ IV, day 1~3) and etoposide(100 $mg/m^2$ IV, day 1~3). In patients with limited disease, after completion of 6 cycles of PVP chemotherapy, chest and prophylatic brain irradiation was performed in case of complete responder, chest irradiation on1y in partial responder. Results: 1) Of 55 evaluable patients, 13(24%) had a complete response and 29(53%) had a partial response. 2) The median survival time was 55.8 weeks for all patients(N=55), 61.1 weeks for limited disease(N=31), 51.3 weeks for extensive disease(N=24). 3) The response duration was 29.1 weeks for responders(N=42). 4) There was no significant prognostic factors influencing response rates. 5) The toxicity was tolerable and there was no treatment-related deaths. Conclusion: The PVP combination chemotherapy as a first-line therapy was effective and well-tolerated in patients with small cell lung cancer.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.40 no.4
• /
• pp.486-492
• /
• 2011

This study was designed to evaluate the effect of hot water extract (ESW) and 70% ethanol extract (ESE) from Euphorbia supina Rafin on LPS-stimulated inflammatory response in RAW 264.7 macrophages. Upon investigation at concentrations up to $1000\;{\mu}g$/mL, ESW and ESE did not have any cytotoxic effects on RAW 264.7 macrophages. ESW induced inhibition of 21.6%~54.8% of nitric oxide (NO) production at 100~1000${\mu}g$/mL, and $PGE_2$ production was inhibited up to 25.7%~38.2% at 250~1000${\mu}g$/mL, proportional to the ESW concentrations. ESW induced inhibition of 66.1% and 54.3% of IL-6 production at 250 and $1000\;{\mu}g$/mL, respectively. ESE (100~1000${\mu}g$/mL) induced inhibition of 38.3%~77.5% of NO, 40%~94.7% of $PGE_2$, and 43.9%~89.4% of IL-6 production, proportional to the ESE concentrations. Only 44.1% of IL-10 production was inhibited at a concentration of $500\;{\mu}g$/mL. ESE induced an increase in TNF-${\alpha}$ production at a concentration of 100 and $250\;{\mu}g$/mL, whereas at high concentrations (500 and $1000\;{\mu}g$/mL), ESE induced inhibition of 19.2% and 92.4% of TNF-${\alpha}$ production, respectively. In conclusion, concentrations of more than $500\;{\mu}g$/mL ESE demonstrated effective immune-modulating activity through inhibition of NO, $PGE_2$, IL-6, IL-10, or TNF-${\alpha}$ production, as it relates to the macrophage's immuno-activity; therefore, ESE has potential as a good candidate substance for reduction of inflammatory responses.