Natural Products Research Institute

Seoul, South Korea

Natural Products Research Institute

Seoul, South Korea
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Yoo H.,Catholic University of Korea | Lee Y.S.,Catholic University of Korea | Lee S.,Seoul National University | Kim S.,Seoul National University | And 2 more authors.
Phytotherapy Research | Year: 2012

Melanoma cells are relatively resistant to apoptosis compared with other tumor cell types, and thus, chemotherapy, radiotherapy and immunotherapy are not effective in treating melanoma. Pachastrissamine (PA) exhibits cytotoxic activity and promotes apoptosis in several cancer cells. However, its specific molecular mechanisms have not been characterized fully. This study investigated the antimelanoma effect of PA, an anhydrophytosphingosine derived from marine sponge, and its underlying molecular mechanisms. The data demonstrated that treatment with PA inhibited the phosphorylation of ERK and subsequent ERK-mediated FOXO3 phosphorylation in melanoma cells. Interestingly, PA did not inhibit AKT-mediated FOXO3 phosphorylation. Therefore, it appears that PA-induced apoptosis results from the inhibition of ERK. Furthermore, intravenous administration of PA was found to suppress melanoma cell growth in a C57BL6 mouse without causing side effects. Additionally, PA inhibited the production of Cdk2, which is involved in cell cycle regulation. Taken together, inhibition of melanoma cell growth by PA is a result of the inhibition of ERK-mediated FOXO3 downregulation and decreased Cdk2 levels. The results of this study imply that dual inhibition of the ERK pathway and cell cycle progression could be an effective approach to control the growth of melanoma cells. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd.

Fan T.-P.,University of Cambridge | Deal G.,Global Regulatory Services | Koo H.-L.,River Cam International | Rees D.,Salupont Consulting | And 14 more authors.
Journal of Ethnopharmacology | Year: 2012

Ethnopharmacological relevance: GP-TCM is the first EU-funded Coordination Action consortium dedicated to traditional Chinese medicine (TCM) research. One of the key deliverables of the Work Package 7 in GP-TCM was to investigate information of the existing requirements for registration of TCM products listed by global regulatory bodies. The paper aims to collate data and draw comparison of these regulations. Case studies are also presented to illustrate the problems involved in registering TCM products in different regions worldwide. Materials and methods: A collaborative network task force was established during the early stage of the GP-TCM project and operated through exchanges, teleconferences and focused discussions at annual meetings. The task force involved coordinators, academics who are actively involved with R&D of Chinese herbal medicines, experts on monographic standards of Chinese materia medica, representatives from regulatory agencies, experts from industries in marketing Chinese medicines/herbal medicines and natural products. The co-ordinators took turns to chair teleconferences, led discussions on specific issues at AGM discussion sessions, at joint workshops with other work-packages such as WP1 (quality issues), WP3 (toxicology issues) and WP6 (clinical trial issues). Collectively the authors were responsible for collating discussion outcomes and updating written information. Results: A global overview of regulations on herbal registration has been compiled during the three years of the consortium. The regulatory requirements for registration of herbal products in the EU and China were compared, and this is extended to other regions/countries: Africa, Australia, Brazil, Canada, Japan, Russia, South Korea, Taiwan, and the United States. A wide variation of the regulations for the categories of herbal products exists: food (functional food, novel foods, dietary food for special medical purpose, foods for particular nutritional use, food supplement); cosmetic, traditional herbal medicine products; herbal medicines for human use and veterinary use. Conclusion: The regulatory issues for registration of herbal products are complicated among the countries and regions worldwide. The information summarised in the text is for reference only. Some regulations which are presented in this review are still in legislation process and may change in due course. Before taking any regulatory action, readers are advised to consult current official legislation and guidance and/or to seek appropriate professional advice. The lessons learnt from global regulation of TCM will provide valuable insights for regulation of other traditional medicine such as Ayurveda and Unani medicine, as well as other forms of indigenous medicine. The WHO is well placed to co-ordinate a consultation process with the aim of putting forward suggestions for harmonisation to key regulatory agencies. © 2012 Elsevier Ireland Ltd. All rights reserved.

Oh K.-B.,Seoul National University | Nam K.-W.,Natural Products Research Institute | Ahn H.,Natural Products Research Institute | Shin J.,Natural Products Research Institute | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2010

Sortase enzymes belong to a family of transpeptidases found in Gram-positive bacteria. Sortase is responsible for the reaction that anchors surface protein virulence factors to the peptidoglycan cell wall of the bacteria. The compound (Z)-3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile (DMMA) has previously been reported as a novel sortase inhibitor in vitro, but the in vivo effects of DMMA have not been studied. Here, we evaluated the in vivo effects of DMMA against infection by wild-type and sortase A- and/or sortase B-deficient Staphylococcus aureus in Balb/c mice. With DMMA treatment, survival rates increased and kidney and joint infection rates decreased (p < 0.01) in a dose-dependent manner. The rate of kidney infection was significantly reduced in the mice treated with sortase A knock-out S. aureus (p < 0.01). These results indicate that by acting as a potent inhibitor of sortase A and moderate inhibitor of sortase B, DMMA can decrease kidney and joint infection rates and reduce mortality in mice infected with S. aureus. These findings suggest that DMMA is a promising therapeutic compound against Gram-positive bacteria. © 2010 Elsevier Inc. All rights reserved.

Jo W.S.,Korea Institute of Radiological and Medical Sciences | Yang K.M.,Korea Institute of Radiological and Medical Sciences | Choi Y.J.,Korea Institute of Radiological and Medical Sciences | Jeong C.H.,Natural Products Research Institute | And 5 more authors.
Molecular and Cellular Toxicology | Year: 2010

Pegmatite is a coarse-grained intrusive igneous rock rich in rare elements such as uranium, tungsten, and tantalum with Ca, K, Mg, Fe, Se, Ge, and Ho. We tested in vitro and in vivo assays for the anti-inflammatory activity of pegmatites. We firstly evaluated the suppressive effects of pegmatite on macrophage cell line RAW 264.7 cells stimulated with proinflammatory stimuli lipopolysaccharide (LPS) to determine nitric oxide (NO) production and TNF-α and IL-6 release. The IC50 values of pegmatite exceeded 5,000 μg/mL. Treatment of RAW 264.7 cells with pegmatite significantly inhibited LPS-stimulated NO production and proinflammatory cytokines such as TNF-α and IL-6 secretion in a dose-dependent manner (P<0.05). In vivo studies were tested with two animal models of arachidonic acid-induced mouse ear edema and an acetic acid-induced increase in capillary permeability. The pegmatite significantly attenuated ear edema induced by arachidonic acid and reduced the acetic acid-induced increase in capillary permeability in mice (P<0.05) when the pegmatite was administered topically (10 mg per ear) for 24 h. Therefore, pegmatite potentially shows an anti-inflammatory activity in the in vitro and in vivo mice and in the development of newer anti-inflammatory agents as mineral materials. © 2010 The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Netherlands.

Zeng X.,Harvard University | Sigoillot F.,Harvard University | Gaur S.,Harvard University | Choi S.,Harvard University | And 7 more authors.
Cancer Cell | Year: 2010

Microtubule inhibitors are important cancer drugs that induce mitotic arrest by activating the spindle assembly checkpoint (SAC), which, in turn, inhibits the ubiquitin ligase activity of the anaphase-promoting complex (APC). Here, we report a small molecule, tosyl-L-arginine methyl ester (TAME), which binds to the APC and prevents its activation by Cdc20 and Cdh1. A prodrug of TAME arrests cells in metaphase without perturbing the spindle, but nonetheless the arrest is dependent on the SAC. Metaphase arrest induced by a proteasome inhibitor is also SAC dependent, suggesting that APC-dependent proteolysis is required to inactivate the SAC. We propose that mutual antagonism between the APC and the SAC yields a positive feedback loop that amplifies the ability of TAME to induce mitotic arrest. © 2010 Elsevier Inc.

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