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Efferth T.,Johannes Gutenberg University Mainz | Banerjee M.,Johannes Gutenberg University Mainz | Paul N.W.,Johannes Gutenberg University Mainz | Abdelfatah S.,Johannes Gutenberg University Mainz | And 49 more authors.
Phytomedicine | Year: 2016

Background Biopiracy mainly focuses on the use of biological resources and/or knowledge of indigenous tribes or communities without allowing them to share the revenues generated out of economic exploitation or other non-monetary incentives associated with the resource/knowledge. Methods Based on collaborations of scientists from five continents, we have created a communication platform to discuss not only scientific topics, but also more general issues with social relevance. This platform was termed 'PhytCancer -Phytotherapy to Fight Cancer' (www.phyt-cancer.uni-mainz.de). As a starting point, we have chosen the topic "biopiracy", since we feel this is of pragmatic significance for scientists working with medicinal plants. Results It was argued that the patenting of herbs or natural products by pharmaceutical corporations disregarded the ownership of the knowledge possessed by the indigenous communities on how these substances worked. Despite numerous court decisions in U.S.A. and Europe, several international treaties, (e.g. from United Nations, World Health Organization, World Trade Organization, the African Unity and others), sharing of a rational set of benefits amongst producers (mainly pharmaceutical companies) and indigenous communities is yet a distant reality. In this paper, we present an overview of the legal frameworks, discuss some exemplary cases of biopiracy and bioprospecting as excellent forms of utilization of natural resources. Conclusions We suggest certain perspectives, by which we as scientists, may contribute towards prevention of biopiracy and also to foster the fair utilization of natural resources. We discuss ways, in which the interests of indigenous people especially from developing countries can be secured. © 2015 Elsevier GmbH. All rights reserved. Source

Kang M.J.,University of Arizona | Wu T.,University of Arizona | Wijeratne E.M.K.,Southwest Center for Natural Products Research and Commercialization | Lau E.C.,University of Arizona | And 7 more authors.
ChemBioChem | Year: 2014

Access to lead compounds with defined molecular targets continues to be a barrier to the translation of natural product resources. As a solution, we developed a system that uses discrete, recombinant proteins as the vehicles for natural product isolation. Here, we describe the use of this functional chromatographic method to identify natural products that bind to the AAA+ chaperone, p97, a promising cancer target. Application of this method to a panel of fungal and plant extracts identified rheoemodin, 1-hydroxydehydroherbarin, and phomapyrrolidoneA as distinct p97 modulators. Excitingly, each of these molecules displayed a unique mechanism of p97 modulation. This discovery provides strong support for the application of functional chromatography to the discovery of protein modulators that would likely escape traditional high-throughput or phenotypic screening platforms. © 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Liu X.,Arizona Cancer Center | Qi W.,Arizona Cancer Center | Cooke L.S.,Arizona Cancer Center | Kithsiri Wijeratne E.M.,Southwest Center for Natural Products Research and Commercialization | And 4 more authors.
Cancer Investigation | Year: 2011

Withaferin A (WA) (1) and two analogs [4-epi-withaferin A (2) and 4,27-diacetyl-4-epi-withaferin A (3)] were evaluated for antitumor activity in pancreatic cancer cells. IC50 for 1, 2, and 3 were 0.87, 0.45, and 0.29 μM (BxPC-3); 1.28, 1.53, and 0.52 μM (MIAPaCa-2); and 0.59, 2.25, and 0.56 μM (PANC-1), respectively. We chose WA analog 3 for functional studies with confirmatory RT-PCR and Western blotting. ANOVA identified 33 (MIAPaCa-2), 54 (PANC-1), and 48 (BxPC-3) gene expression changes. Fisher exact test demonstrated MAPK and glutathione pathways to be overexpressed with WA analog 3. WA analog 3 elicits a dose-and time-dependent apoptosis, activates MAPK and glutathione "stress" pathways, and inhibits proliferation. © 2011 Informa Healthcare USA, Inc. Source

Hoffman M.T.,University of Arizona | Gunatilaka M.K.,University of Arizona | Wijeratne K.,Southwest Center for Natural Products Research and Commercialization | Gunatilaka L.,Southwest Center for Natural Products Research and Commercialization | Arnold A.E.,University of Arizona
PLoS ONE | Year: 2013

Numerous plant pathogens, rhizosphere symbionts, and endophytic bacteria and yeasts produce the important phytohormone indole-3-acetic acid (IAA), often with profound effects on host plants. However, to date IAA production has not been documented among foliar endophytes -- the diverse guild of primarily filamentous Ascomycota that live within healthy, above-ground tissues of all plant species studied thus far. Recently bacteria that live within hyphae of endophytes (endohyphal bacteria) have been detected, but their effects have not been studied previously. Here we show not only that IAA is produced in vitro by a foliar endophyte (here identified as Pestalotiopsis aff. neglecta, Xylariales), but that IAA production is enhanced significantly when the endophyte hosts an endohyphal bacterium (here identified as Luteibacter sp., Xanthomonadales). Both the endophyte and the endophyte/bacterium complex appear to rely on an L-tryptophan dependent pathway for IAA synthesis. The bacterium can be isolated from the fungus when the symbiotic complex is cultivated at 36°C. In pure culture the bacterium does not produce IAA. Culture filtrate from the endophyte-bacterium complex significantly enhances growth of tomato in vitro relative to controls and to filtrate from the endophyte alone. Together these results speak to a facultative symbiosis between an endophyte and endohyphal bacterium that strongly influences IAA production, providing a new framework in which to explore endophyte-plant interactions. © 2013 Hoffman et al. Source

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