Keynote Conference - Interevent

Symp #28 Cells as biosensors
Chairs Glaucia M Machado Santelli and Paulo Saldiva
Cytotoxic indole alkaloids isolated from Duroia macrophylla (Rubiaceae).
Cecilia Veronica Nunez 1 *, Marne Carvalho de Vasconcellos 2 , Vincent Roumy 3 , Sevser Sahpaz 3 , François Bailleul 3 , Thierry Hennebelle 3 .
1
Laboratório de Bioprospecção e Biotecnologia, Coordenação de Tecnologia e Inovação, Instituto Nacional de Pesquisas da Amazônia,
Aleixo, Manaus, Amazonas, 69060-001, Brazil;
2
Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas – UFAM, Rua Alexandre Amorim, 330, Aparecida, Manaus,
Amazonas, 69010-330, Brazil;
3
Laboratoire de Pharmacognosie, EA 4481, Université de Lille 2 – Droit e Santé, 59006, Lille, France.
Duroia macrophylla Huber is a native plant species of the Amazon region. It is known as cabeça-de-urubú, apuruí or puruí-grande-damata
but no medicinal use is described for it. In our research group bioprospection programm, we collected several Rubiaceae plant
species, prepare organic and aqueous extracts and assayed to several activities. D. macrophylla extracts were first assayed against
Artemia salina, to determine their toxicity. The methanolic leaf extracts was toxic against A. salina, with a LD50 of 40.00 µg/mL. Then,
the methanolic leaf extract was fractionated and 4 alkaloids were isolated: two new roxburguine indole alkaloids plus two other
known ones. All isolated substances were essayed on tumor cell lines and the new alkaloid 4 showed a cytotoxic activity against HL60
(human leukemia), APC02 (human gastric adenocarcinoma) and B16F10 (murine melanoma) tumor cell lines (IC50 values of 2.28
µg/mL, 5.08 µg/mL and 5.11 µg/mL, respectively) and a cytotoxicity of 7.8 µg/mL on normal cell line NHI3T3 (fibroblast murine). The
alkaloids assayed did not cause membrane disruption in mouse erythrocytes. This is the first chemical study on this species. Our
findings showed that Amazonian plant species can contain new active substances, even if they do not have popular use.
Acknowledgments: CT-Agro/CNPq, PPBio/CNPq, FAPEAM, INCT - CENBAM/CNPq.
Cell-fiber interactions: effects on cell biology
Glaucia Maria Machado-Santelli
(glaucia.usp@gmail.com) Department of Cell and Developmental Biology Institute of Biomedical Sciences - University of São Paulo,
Brazil
Particle toxicology main subject is to understand their cytotoxic and genotoxic mechanisms. Initial studies focused on the evaluation
of particles parameters after inhalation such as the diameter, length and biopersistence led to the association of asbestos exposure
with several health problems including lung cancer and mesothelioma. The low biopersistence of chrysotile, causing it to disintegrate
and become shorter in the lungs, is the main structural features that lead the chrysotile being less pathogenic than the amphiboles.
This safety has been controversial since in vitro chrysotile-associated genotoxic potential has been demonstrated. We evaluated the
induction of micronucleated, poliploid and multinucleated cells in chrysotile exposed cultured cells. These in vitro studies show that
fibers interfere with mitoses and cytokinesis progression leading to multinucleated and polyploid cells. Cell cycle progression is
impaired by fibers and multipolar mitosis may be consequence of fiber induced centrosomic amplification. The cell fate was followed
by pulse-time microscopy, allowing us to establish how the chrysotile treatment acts on cell cycle progression and its possible
relation with other types of fibers.
Cellular responses to ambient levels of air pollution
Paulo Saldiva
(pepino@usp.br) Department of Pathology Faculty of Medicine – University of São Paulo, Brazil
The widespread use of fossil fuels has been associated to marked alterations in our environmental. Global climate changes and local
air pollutants are known to cause adverse health effects in humans. The use of cells as biosensors of adverse effects have provided
valuable information for the process of evaluating environmental risk associated to air pollution. Respiratory epithelium,
endothelium, placental trophoblast, cells of seminiferous tubules, endometrium, and cells of reproductive organs of higher plants
have been extensively used to detect, quantify and explore the mechanisms of pollution induced injury, disclosing new perspectives
to the process of pollution control, aimed to preserve human health. Effects of air contaminants such as endocrine disruption,
cardiovascular damage, cancer induction and promotion and persistent inflammation, have been characterized using cellular systems
or in vivo toxicological approaches. In this context, biomonitoring of air pollution is nowadays as important as the classical chemical
characterization of the concentration of environmental toxics, opening new areas of research in cell biology.
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