• Title/Summary/Keyword: First-in-human dose

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Citrinin Hydrate Inhibit Serotonin N-Acetyltransferase Catalyzing the Conversion of Serotonin to N-Acetylserotonin

  • Lee, In-Kyoung;Yun, Bong-Sik;Kim, Kyong-Tai;Choi, Bo-Hwa;Park, Tae-Ju;Kim, Young-Ho;Yoo, Ick-Dong
    • Journal of Microbiology and Biotechnology
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    • v.11 no.6
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    • pp.1099-1101
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    • 2001
  • In an attempt to search for serotonin N-acetyltransferase (arylalkylamine N-acetyltransferasem, AA-NAT) inhibitors from microbial metabolites, we fecund the culture broth of Penicillium sp. 80722 which showed a strong inhibitory activity against AA-NNT. The active principle has been identified as citrinin hydrate through bioassay-guided fractionation of cultural broth, and structure elucidation derived by spectroscopic analyses. Citrinin hydrate inhibits AA-NAT with an $IC_50$ value of $173{\mu}M$ in a dose-dependent manner. Although citrinin hydrate was previously isolated as human rhinovirus 3C-protease inhibitor, this was recognized as the first AA-NAT inhibitor isolated from natural sources.

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Ulva lactuca : A Potential Seaweed for Tumor Treatment and Immune Stimulation

  • Lee, Dong-Geun;Hyun, Jin-Won;Kang, Kyong-Ah;Lee, Jin-Ok;Lee, Sang-Hyun;Ha, Bae-Jin;Ha, Jong-Myung;Lee, Eun-Yeol;Lee, Jae-Hwa
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.9 no.3
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    • pp.236-238
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    • 2004
  • This is the first report on the antitumor and immunostimulating activities of Ulva lactuca. Using the WSM (water-soluble fraction of a methanol extract from Ulva lactuca), a concentration of 140 g/mL was found to inhibit 50% of the human leukemia cell line U937 in growth, while splenocyte growth was stimulated up to a concentration of 100$\mu\textrm{g}$/mL. In addition, NO production by a macrophage cell line (RAW 264.7) and alkaline phosphatase activity in mouse splenocytes were both stimulated with 10$\mu\textrm{g}$/mL of WSM. Dose-dependent patterns were observed on all three cell-lines. Accordingly, the current results indicate that VUlva lactuca may be useful as a natural antitumor and immunostimulating agent.

Effects of Chenopodium album Linne on Gastritis and Gastric Cancer Cell Growth

  • Kim, Pitna;Jeong, Choon-Sik
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.487-492
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    • 2011
  • In our previous study, we investigated Chenopodium album Linne (CAL) ethanol extract and its fractions on anti-gastritic actions using the HCl/ethanol and indomethacin induced gastric lesion model and Helicobacter pylori (H. pylori). Based on the results, butanol fraction was most effective among fractions obtained from CAL. This study aims to elucidate the mechanisms of butanol fraction, and betaine as a constituent of the butanol fraction, on gastritis and anti-gastric cancer cell growth. First, we examined antioxidant properties using hydrogen peroxide and superoxide radical, and we found that butanol fraction and betaine may be good antioxidants. Second, cytotoxicity was assessed by measuring cell viability and 4,6-diamidino-2-phenylinodole dihydrochloride (DAPI) staining of human gastric cancer cells (AGS cells). We also examined the relationship between the cytotoxicity and intracellular $Ca^{2+}$ signaling mechanism. The butanol fraction demonstrated cell viability 71.49% at the concentration of 100 ${\mu}g/ml$ and increased intracellular $Ca^{2+}$ concentration in a dose dependent manner. Finally, we observed the mucus content as a defensive factor and gastric secretion as an aggressive factor, and found that the mucus content noticeably increased when treated with butanol fraction and betaine and gastric secretion decreased when treated with betaine in vivo study. From these results, we suggest that CAL butanol fraction and betaine may have protective effects on gastritis.

Latex of Ficus carica L. Induces Apoptosis Through Caspase and Bcl-2 Family in FaDu Human Hypopharynx Squamous Carcinoma Cells

  • Shin, Bo Su;Lee, Seul Ah;Moon, Sung Min;Han, Seul Hee;Hwang, Eun Ju;Kim, Su-Gwan;Kim, Do Kyung;Kim, Jin-Soo;Park, Bo-Ram;Kim, Chun Sung
    • International Journal of Oral Biology
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    • v.42 no.4
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    • pp.183-190
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    • 2017
  • Ficus carica L. (common fig), one of the first plants cultivated by humans, originated in the Mediterranean basin and currently grows worldwide, including southwest Asia and South Korea. It has been used as a traditional medicine for treatment of metabolic, cardiovascular, and respiratory diseases as well as hemorrhoids and skin infections. Its pharmacological properties have recently been studied in detail, but research on the anti-cancer effect of its latex has been only been studied on a limited basis on several cell lines, such prostate cancer, breast cancer, and leukemia. In this study, we investigated the anti-cancer activity of the latex of Ficus carica L.and its underlying mechanism in FaDu human hypopharynx squamous carcinoma cells. (See Ed. note above) We confirmed through SDS-PAGE analysis and gelatinolytic activity analysis that the latex of Ficus carica contains cysteine protease ficin. Our data showed that the latex inhibited cell growth in a dose-dependent manner. In addition, the latex treatment markedly induced apoptosis in FaDu cells as determined by FACS analysis, elevated expression level of cleaved caspase-9, -3 and PARP (poly (ADP-ribose) polymerase), and. increased the expression of Bax (pro-apoptotic factor) while decreasing the expression of Bcl-2 (anti-apoptotic factor). Taken together, these results suggested that latex containing the ficin inhibited cell growth and induced apoptosis by caspase and the Bcl-2 family signaling pathway in FaDu human hypopharynx squamous carcinoma cells. These findings point to the potential of latex of Ficus carica to provide a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.

Two cabob of natural human infection by Echinostoma hoytense and its second intermediate horst in Wonju area (Echinostoma hortense 인체감염 2예 및 제이중간숙주 조사)

  • 양용석;안영겸
    • Parasites, Hosts and Diseases
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    • v.23 no.1
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    • pp.33-40
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    • 1985
  • Two cases of human Erhinostoma hortense infection and their probable infection source were identified by prasiqantel (Distocide) treatment of the patients and by examining two kinds of fresh water fish which were eaten raw by them. The result of the research can be summarized as follows: 1. The patients, each aged 31 and 30, were residing in the same house in Wonju City, Kangwon Province. The first case was hospitalized due to epidemic hemorrhagic fever (E.H. fever) and the second case was healthy but had slight degree of abdominal pain and diarrhea from time to time. In the stool examination, eggs of 5. hortense ($114.3{\times}71.0{\mu\textrm{m}}$) average from the first case and $119.1{\times}68.3{\mu\textrm{m}}$ average from the second) were found. By administering single dose of praziquantel (10~15mg/kg) and purgation with magnesium salt to them. sin adults of 5. hortense were collected from the diarrheal stools of the second case. 2. By examining 8:k Moroco oxycephalus and 20 Carassius carassius which were captured at the place where the two patients had captured and eaten the fresh water fish, the metacercariae of Echinostoma sp. were found from 3 (3.5%) M. oxycephalus. 3. After the experimental infection of 3 isolated metacercariae to one albino rat three adults of 5. hortense were recovered. By the present study, the two patients revealing the echinostomatid eggs in their stools were proven to be infected with 5. hortense and to be the second and third human cases of this luke infection in Korea. Mcroco oxycephalus harboured the metacercariae of E. hortense and appeared to be a new second intermediate host.

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Inducible Expression of the Lactadherin Gene with a Reverse Tetracycline-Regulated Retroviral Vector System (Tetracycline으로 발현이 유도되는 Retrovirus Vector System을 이용한 Human Lactadherin 유전자의 전이와 발현)

  • 이용석;오훈규;권모선;박창식;김태완;박재복
    • Korean Journal of Animal Reproduction
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    • v.27 no.3
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    • pp.259-268
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    • 2003
  • Lactadherin (formerly known as BA46), a major glycoprotein of the human milk fat globule membrane, is abundant in human breast milk and breast carcinoma cells and is known to prevent symptomatic rotavirus infections. In this study, we tried to transfer the human lactadherin gene to the Chinese Hamster Ovary (CHO) cells using retrovirus vector system and tested inducible expression of the gene under the tetracycline-controllable promoter. At first, tetracycline-mediated inducibility was tested using E.coli LacZ marker gene. NIH3T3 cells co-infected with RevTet-On and RevTRE-LacZ retrovirus vectors showed that the cells responded to doxycycline (a derivative of tetracycline) in a dose-dependent manner, and prominent induction of the lacZ gene expression was observed from 1 $\mu\textrm{g}$/ml of doxycycline concentration. Based on the results of the pilot experiment, inductional expression of the human lactadherin gene was conducted using RevTet-On and RevTRE-Ltd retrovirus vectors. Analysis with the RT-PCR demonstrated successful inductional expression of the lactadherin gene in the Chinese Hamster Ovary (CHO) cells. Considering that constitutive overexpression of the exogenous genes in the target cells causes serious physiological imbalance, the results obtained in this study will be very useful especially in the studies of gene therapy and transgenic animal production.

Functional analysis of the antioxidant activity of immune-challenged Bombyx mori hemolymph extracts in the human epithelial Caco-2 cell line

  • Kim, Seong Ryul;Kim, Kee-Young;Kim, Seong-Wan;Park, Seung-Won
    • International Journal of Industrial Entomology and Biomaterials
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    • v.40 no.1
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    • pp.16-21
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    • 2020
  • Humans use insects as food and traditional medicine for many years. Hemolymph is the circulating fluid of insects and is a key component of their immune system. However, limited information is available regarding hemolymph identification, development, and differentiation, as well as the related cellular immune responses. In a previous study, hemolymph extracts prepared from Bombyx mori larvae were found to exert anti-inflammatory effects. In this study, we aimed to identify and compare the antioxidant activity of immune-challenged and unchallenged B. mori hemolymph extracts in vitro. For this purpose, human epithelial Caco-2 cells were first exposed to oxidative stress and then treated with various concentrations and incubation times of either immune-challenged or unchallenged B. mori hemolymph extracts. Next, we determined the effect of treatment on the relative expression of GPX-1, SOD-1, and SOD-2 antioxidant marker genes. We found that the expression rates of the three marker genes were markedly higher at a immune-challenged hemolymph extract concentration of 80 ppm compared to those at other concentrations, and the antioxidant effects were enhanced after treatment for 48 hr. Thus, B. mori hemolymph extracts showed antioxidant activity within the limited time and dose. Especially, the immune-challenged B. mori hemolymph extracts showed higher the antioxidant activities than unchallenged one. The activity of silkworm hemolymph extracts could facilitate the development of new types of functional foods, feed additives, and biomaterials with antioxidant properties.

Apoptotic Activity of Insect Pathogenic Fungus Paecilomycesc japonica Toward Human Acute Leukemia Jurkat T Cells is Associated with Mitochondria-Dependent Caspase-3 Activation Regulated by Bcl-2

  • Park, Hye-Won;Jen, Do-Youn;Kim, Young-Ho
    • Journal of Microbiology and Biotechnology
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    • v.12 no.6
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    • pp.950-956
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    • 2002
  • The antitumor activity of the insect pathogenic fungus Paecilomyces japonica has been attributed to apoptotic cell death. However, the mechanism underlying the induced apoptosis has not yet been elucidated. In this study, we for the first time show that mitochondria-dependent caspase-3 activation were associated with the apoptotic activity of P. japonica in human acute leukemia Jurkat T cells. When Jurkat T cells were treated with the ethyl acetate extract of P japonica at concentrations ranging from $2-6{\mu}g/ml$, apoptotic cell death. accompanied by several biochemical events such as caspase-9 activation, caspase-3 activation, degradation of poly (ADP-ribose) polymerase (PARP), and apoptotic DNA fragmentation, was induced in a dose-dependent manner. In addition, the release of cytochrome c from mitochondria was detected. Under these conditions, the expression of Fas and Fas-ligand (FasL) remained unchanged. Ethyl acetate extract-induced mitochondrial cytochrome c release, caspase-3 activation, PARP cleavage, and apoptotic DNA fragmentation were suppressed by the ectopic expression of Bcl-2, which is known to block mitochondrial cytochrorme c release. Accordingly, these results demonstrate that P. japonica-induced apoptotic cell death is mediated by a cytochrome c-dependent caspase-3 activation pathway that can be interrupted by Bcl-2.

Effects of Garlic Oil on Pancreatic Cancer Cells

  • Lan, X.Y.;Sun, H.Y.;Liu, J.J.;Lin, Y.;Zhu, Z.Y.;Han, X.;Sun, X.;Li, X.R.;Zhang, H.C.;Tang, Z.Y.
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5905-5910
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    • 2013
  • Background: To investigate the preventive and therapeutic potential of garlic oil on human pancreatic carcinoma cells. Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was performed to study the effects of garlic oil on three human pancreatic cancer cell lines, AsPC-1, Mia PaCa-2 and PANC-1. Cell cycle progression and apoptosis were detected by flow cytometry (FCM), staining with PI and annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI), respectively. Morphologic changes of pancreatic cancer cells were observed under transmission electron microscopy (TEM) after treatment with garlic oil at low inhibitory concentrations ($2.5{\mu}M$ and $10{\mu}M$) for 24 hours. Results: Proliferation of the AsPC-1, PANC-1, and Mia PaCa-2 cells was obviously inhibited in the first 24 hours with the MTT assay. The inhibition effect was more significant after 48 hours. When cells were exposed to garlic oil at higher concentrations, an early change of the apoptotic tendency was detected by FCM and TEM. Conclusion: Garlic oil could inhibit the proliferation of AsPC-1, PANC-1, and Mia PaCa-2 cells in this study. Moreover, due to programmed cell death, cell cycle arrest, or both, pro-apoptosis effects on AsPC-1 cells were induced by garlic oil in a dose and time dependent manner in vitro.

Imyosan induces caspases-mediated apoptosis in human colorectal cancer HCT116 cells (이묘산(二妙散)에 의한 대장암 세포주 HCT116의 Caspases 활성화를 매개로 한 세포사멸)

  • Kim, Sun-Mo;Yun, Hyun-Jeung;Lee, Hyun-Woo;Kim, Pan-Jun;Lee, Chang-Hyun;Park, Won-Hwan;Park, Sun-Dong
    • Herbal Formula Science
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    • v.14 no.2
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    • pp.21-32
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    • 2006
  • The purpose of this study was to investigate the effect of Imyosan on apoptosis in human colorectal cancer HCT116 cells. Phellodendron amurense Rupr. and Atratylodes lancea D.C. compose Imyosan. First of all, to study the cytotoxic effect of methanol extract of Imyosan (IMS-MeOH) on HCT116 cells, the cells were treated with various concentrations of IMS-MeOH and then cell viability was determined by XTT reduction method. IMS-MeOH reduced viability of HCT116 cells in a dose and time-dependent manner. To confirm the induction of apoptosis, the c1eavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of caspase-3, procaspase-8 and procaspase-9 were examined by western blot analysis. IMS-MeOH decreased procaspase-3, procaspase-8 and procaspase-9 levels in a dose-dependent manner and induced the clevage of PARP. IMS-MeOH triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome c from mitochondria to cytosol. Furthermore, IMS-MeOH also downregulated the anti-apoptotic Bcl-2 and upregulated the pro-apoptotic-Bax. Therefore, these results suggest that IMS-MeOH induced HCT1l6 cell death through the mitochondrial pathway. To explore whether the activities of caspases was required for induction of apoptosis by IMS-MeOH, caspase-3, -8, -9 activity measured by using substrates, respectively. IMS-MeOH increased caspase-3, -8, -9 activity. Co-treatment with inhibitors of caspase-3, -8, -9 and IMS-MeOH significantly blocked IMS-MeOH-triggered apoptosis in HCT1l6 cells. These results suggest that IMS-MeOH induces caspases-mediated apoptosis.

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