This thesis addresses an under-researched disjunction surrounding knowledge creation between, and within, development and pastoralist groups. Many academics increasingly recognise pastoralist populations as creative and adaptable, yet these populations often lack the resources to develop innovations beyond the local context. Despite often being better resourced than pastoralist communities, development interventions in the Horn of Africa have achieved limited successes; an observation often linked in academic literature with a failure to rethink inappropriate established practices drawn from settled agriculture. The need to explore new ways of understanding hybrid knowledge creation in pastoralist settings emerged from the international community's limited understanding of informal innovation processes and unique contexts of pastoralist regions, due in part to the unsuitability of current frameworks and research tools for conceptualising informal innovation in marginal settings. This study makes an original research contribution by exploring the factors that shape processes of knowledge creation between development and pastoralist groups to answer the question what factors influence innovation in pastoralist areas? An interconnected, mixed-methods research strategy was developed and applied to study the role of knowledge networks and framings in processes of knowledge creation amongst pastoralist and development actors innovating in North Horr, Kenya. The empirical data gathered throughout the research informed the development of an internally-valid analytical framework with which to explore innovation in this setting. The key findings of this study highlight the importance of the contextual and often asymmetric nature of relationships in processes of emergent knowledge creation within pastoralist development. The observations collected throughout the research process provide an empirical basis from which to discuss networks, framings, and knowledge creation in pastoralist settings; contributing to wider debates surrounding informal innovation processes and narratives of pastoralist development.

Cholangiocytes, bile duct lining cells, actively adjust the amount of cholesterol and bile acids in bile through expression of enzymes and channels involved in transportation and metabolism of the cholesterol and bile acids. Herein, we report molecular mechanisms regulating bile acid biosynthesis in cholangiocytes. Among the cytochrome p450 (Cyp) enzymes involved in bile acid biosynthesis, sterol 27-hydroxylase (Cyp27) that is the rate-limiting enzyme for the acidic pathway of bile acid biosynthesis expressed in cholangiocytes. Expression of other Cyp enzymes for the basic bile acid biosynthesis was hardly detected. The Cyp27 expression was negatively regulated by a hydrophobic bile acid through farnesoid X receptor (FXR), a nuclear receptor activated by bile acid ligands. Activated FXR exerted the negative effects by inducing an expression of fibroblast growth factor 15/19 (FGF15/19). Similar to its repressive function against cholesterol 7α-hydroxylase (Cyp7a1) expression in hepatocytes, secreted FGF15/19 triggered Cyp27 repression in cholangiocytes through interaction with its cognate receptor fibroblast growth factor receptor 4 (FGFR4). The involvements of FXR and FGFR4 for the bile acid-induced Cyp27 repression were confirmed in vivo using knockout mouse models. Different from the signaling in hepatocytes, wherein the FGF15/19-induced repression signaling is mediated by c-Jun N-terminal kinase (JNK), FGF15/19-induced Cyp27 repression in cholangiocytes was mediated by p38 kinase. Thus, the results collectively suggest that cholangiocytes may be able to actively regulate bile acid biosynthesis in cholangiocytes and even hepatocyte by secreting FGF15/19. We suggest the presence of cholangiocyte-mediated intrahepatic feedback loop in addition to the enterohepatic feedback loop against bile acid biosynthesis in the liver.

The communism unit recommended to Virginia school divisions in 1964 was a part of a major curriculum project sponsored by the State Department of Education and developed over a five-year period of time. In addition to advocating the seven-week unit of study about communism, the government project focused attention on the free enterprise system and modified the traditional structure of the government course. Between 1959 and 1964, the Virginia State Department of Education produced two outline guides and a comprehensive instructional guide to assist teachers in the reorganization of the course. The government project officially began in the summer of 1959 when the State Board of Education requested the State Department of Education to develop an instructional unit on the free enterprise system. Davis Y. Paschall, Superintendent of Public Instruction, appointed a committee, consisting of a local school district director of instruction and secondary teachers of government and economics, to work with the staff of the State Department of Education in developing the unit. The committee, known as the Teacher Committee, decided that the unit should be included in the twelfth-grade government course and that an outline for the entire course should be prepared. Paschall also appointed a committee, consisting of representatives of business, industry, law, government, and education, to review the work of the staff and the Teacher Committee. The staff, with the assistance of these two committees, developed the outline guide, "Virginia and U. S. Government." The State Board of Education distributed the guide to schools in September, 1960, approximately one year after the initial request had been made concerning economic education. The second phase of the government project began in April, 1961, when the State Board of Education directed the State Department of Education to develop an instructional unit to assist teachers in developing units about communism. The department had received requests for the curriculum to include more instruction about communism, and the first guide had placed little emphasis on it. Both of the committees involved in developing the first outline guide assisted the staff of the department with the second guide. In May, 1961, the State Department of Education issued the second guide, Communism in Contrast With the Principles of American Freedom, to be used in conjunction with the first guide, "Virginia and U. S. Government." During the time of the development of the first two guides, the Commission on Constitutional Government assisted the State Department of Education in the government project. The commission, created by the General Assembly to promote states' rights, offered its assistance to the State Department of Education in promoting the study of constitutional government. As a result of this offer, the department involved the commission in the government project. In the summers of 1960 and 1961, the commission funded the teacher institutes offered by the department to acquaint teachers with the guide, "Virginia and U. S. Government." In 1961, the Commission on Constitutional Government unsuccessfully attempted to produce a manual about communism for student use. When this project was terminated, the commission continued assisting the department by reviewing, recommending, and purchasing books to be used with the second outline guide, Communism in Contrast With the Principles of American Freedom. Beginning in the spring of 1963, staff members of the State Department of Education, assisted by an expanded Teacher Committee and the Review Committee, began work on the final product of the government curriculum project. The third guide, An Instructional Guide for Virginia and United States Government, was a comprehensive instructional guide and an expansion of the two earlier guides. The first two guides provided only brief content outlines while the third guide included an outline for the course, an analysis of recommended content, and an extensive bibliography. A major focus of the third guide was Unit V, “Totalitarianism” in Contrast With the Principles of American Freedom," which provided content for an in-depth study of communism. The guide also provided for detailed study of the American economic system. In November, 1964, the State Board of Education published the third guide and distributed it to local school divisions. Teachers began using the guide in the 1964-1965 school year, five years after the initiation of the government project. / Ed. D.

In a phosphate-buffered (pH 5.7) inorganic salts solution (B), nearly full dependence en exogenous carbon was found for high (90 to 100%) germination of washed, Tween 20-treated conidia of Aspergillus flavus over a range of conidial densities. No exogenous carbon-independent germination was observed for settling tower-deposited dry conidia. At equivalent carbon, an amino acid mixture supported higher germination of washed conidia than a sugar-organic acid-alcohol mixture plus NH₄Cl; proline or alanine alone supported higher germination than several other single amino acids or single sugars plus NH₄Cl tested. Glucose plus NH₄Cl was the most stimulatory of the latter. "Amino acid carry-over" for conidial germination of A. flavus was not confirmed in these studies. When exogenous carbon was supplied as glucose, germination of washed conidia was more dependent, generally, on exogenous nitrogen, supplied as NH₄Cl, as the conidial density increased from 10³ to 10⁵ conidia/ml. At equivalent nitrogen, proline alone, or certain amino acid mixtures supported higher germination than NH₄Cl, KNO₃, or several other single amino acids tested in B solution plus glucose. Percentage germination decreased as the conidial density decreased from 10⁵ to 10³ conidia/nl when glucose plus NH₄Cl were supplied at each density at constant amounts/conidium. A light decrease in percentage germination was observed in glucose plus an amino acid mixture, and a moderate decrease was observed in glucose plus peptone. Percentage germination decreased as conidial density increased from 1 x 10³ to 1 x 10⁵ conidia/ml for each of three concentrations of glucose alone or glucose plus NH₄Cl examined. Removal of CO₂ from the germination medium almost completely inhibited germination and swelling in glucose plus NH₄Cl and suppressed germination in glucose plus an amino acid mixture. Two surfactants increased percentage germination of settling tower-deposited conidia in the presence of glucose plus NH₄Cl and supported low germination in B solution alone. Maximum germination occurred at 35°C in glucose plus NH₄Cl medium, while in glucose plus peptono medium maximum germination occurred at 30°C and 35°C. At 30°C the rate of germination was higher in glucose plus peptone medium than in glucose plus NH₄Cl medium. A broad pH optimum range (pH 3.0 to 7.5) was found for conidial germination using both citrate-phosphate and phosphate buffers containing glucose plus peptone. In glucose plus NH₄Cl a somewhat narrower pH optimum range, was observed. The possible relation of these findings to conidial germination in soil and in the geocarposphere of peanut fruit is discussed. / Ph. D.

This research investigated current consumer attitudes about clothing and textile flammability legislation in relation to socioeconomic class and parental status. One hundred fifty women from six different regions in Virginia participated in this study. Data was collected by telephone interview. There were no statistically significant differences in the responses of women in relation to socio-economic class as determined by the McGuire-White (Short Form). However, the following findings were observed: Upper-middle class respondents were most likely to know about existing flame retardant (FR) standards and to consider FR apparel as "very important" for all ages of children, and adults, 65 years and over. They were least likely to desire FR standards on clothing for adults, ages 15 through 64. Lower-middle class women were most inclined to think there should be FR standards on all clothing, regardless of age of wearer. Women from the upper-lower class were least likely to know about existing FR standards and higher price of these protective textile items; more of these women than any other socio-economic group believed that the government and/or clothing manufacturers should assume the responsibility for protecting consumers from unsafe textile products, while women from the upper middle class were most inclined to think consumers should protect themselves. Analysis of the data was statistically significant for some of the differences in responses when the women were categorized as parents or non-parents. Parents were more likely to consider FR clothing "very important" for adults, 65 and older but less inclined to believe that clothing with FR finishes was "very important" for adults, ages 15 through 64. Parents were also more likely than non-parents to own FR clothing and have knowledge about special care and price of FR textile products. Most respondents had some knowledge of FR standards. The largest proportion of the total sample indicated that they thought there should be FR standards on clothing for all children up to age 14, adults over 65, and disabled and handicapped people. A majority of the women also believed that all consumers should have a choice available in the retail market between FR and regular clothing, especially for those people between the ages of 15 and 64. FR clothing was considered "very important" for all children up to age 14, adults over 65, and disabled and handicapped people by most of the homemakers. Approximately one-third of all respondents had some personal knowledge of fire injuries, owned FR apparel, and were aware that it costs more than regular clothing. A vast majority of the women were willing to pay more for added protection from fabrics which burn easily, and thought the government should check products on the market for safety and should educate the public about fire hazards rather than passing new laws. Government and clothing manufacturers were the two sectors of the economy that most respondents thought should assume the responsibility for protecting consumers from dangerously flammable fabrics and apparel. / Master of Science

An approach for approximating linear time-invariant system models of high order by simplified models of low order is developed. The problem of approximating systems having no unstable modes is investigated first. An iterative scheme for minimizing a quadratic fractional of the error between the system outputs and simplified model outputs is proposed. The computational requirements of the algorithm are reduced by first converting the multiple input system to an equivalent single input system and then choosing a canonical structure for the simplified model. The Schwarz canonical form is selected and advantage is taken of the special properties of the Schwarz form. The simplification of systems having unstable modes is then considered. A technique for decomposing the system model into stable and unstable subsystems is presented. The unstable modes of the system are retained in the simplified model, and the algorithm for reducing the order of stable systems is.applied to the stable subsystem. Finally, the use of simplified models in designing suboptimal output regulators for complex systems is outlined. The suboptimal control scheme is applied to the power system stabilization problem. Two examples of power.system control are given to demonstrate the value of the control scheme. / Master of Science

Today, current drug discovery and lead generation efforts focus on high throughput screening of large chemical libraries as the primary source of lead candidates. A lack of investment in novel chemotype development by pharmaceutical companies over the last 15 years coupled with the concurrent merger of screening collections and the availability of generic compound libraries commercially have resulted in many discovery efforts that lack uniqueness and do not offer a strong patent position to operate. The need for better, more diverse, and more drug-like libraries is essential in order to feed high throughput screening efforts with molecules that probe new dimensions of chemical space and allow for the discovery of untapped intellectual property.This dissertation details a complete structure based study to design novel inhibitors of B-Raf and p38a MAP Kinase. A structural evaluation of the important and similar interactions necessary for DFG-out allosteric inhibitors to bind their respective targets was accomplished through the synthesis and evaluation of three known allosteric kinase inhibitors, Gleevec®, Nexavar®, and BIRB-796, and 8 additional DFG-out allosteric inhibitors that were developed directly from fragments of these successful scaffolds. The structural insight that was gained from the evaluation of known DFG-out allosteric inhibitors was then utilized to design novel inhibitors that incorporated two unique scaffolds based on two new [3+2] cycloaddition reactions.A pyrrolo-3,4-dicarboximide scaffold has been developed through the utilization of a novel tandem [3+2] cycloaddition then elimination reaction scheme. This scaffold, which contains three sites for variation, was then rationally incorporated into lead molecules using structure-based methods and in silico feedback for the production of dual DFG-out allosteric kinase inhibitors of p38a and B-Raf kinase. These inhibitors display micromolar to submicromolar enzymatic IC50's for both p38a and B-Raf kinase and low micromolar inhibition of cell growth in 4 separate cancer cell lines.We also explored new chemistry that utilizes a key one pot, [3+2] cycloaddition reaction to obtain highly substituted imidazoles and their application in the design of specific allosteric B-Raf inhibitors. Inhibitors based on this scaffold display subnanomolar potency and a favorable kinase profile.

Le cœur est un organe central au fonctionnement du système cardiovasculaire. Il est physiologiquement compartimenté et est constitué de cellules spécialisées qui régulent les impulsions électriques ainsi que la contraction du myocarde. Le cœur adapte le flux sanguin en fonction des besoins du corps. En condition pathologique, le cœur recourt toutefois à des mécanismes compensatoires. Au niveau physiologique, la compensation s’observe par l’hypertrophie des cardiomyocytes qui, bien que bénéfique à court terme, exacerbe à long terme la fonction cardiaque. L’activation des « mitogen activated protein kinases » (MAPK) contribue autant au maintien de la fonction physiologique qu’à la détérioration pathologique du myocarde et serait également une cause de l’hypertrophie observée. Parmi les 5 groupes de MAPK connues, la MAPK p38 est formée de 4 isoformes dont les sérine/thréonine kinases p38α et p38γ sont exprimées de façon prédominante dans le cœur. Les p38 partagent les mêmes activateurs, mais leurs effecteurs diffèrent. Bien que le rôle de p38α semble impliqué dans l’aggravement des troubles cardiaques, celui de p38γ ne semble pas redondant à p38α et demeure incompris. Cette isoforme possède un motif de liaison aux domaines PDZ, unique chez les MAP kinases. Également, chez les cellules cardiaques, elle transloque au noyau en condition de stress. Le but de l’étude ici est de comprendre le rôle de p38γ et de ses motifs uniques sur la structure et la taille des cardiomyocytes. Afin de répondre au but de l’étude, plusieurs mutants adénoviraux de p38 ont été conçus. Un des mutants ne possède pas le motif de liaison aux domaines PDZ, deux autres contrôlent la localisation cellulaire soit au noyau, soit au cytoplasme, et un autre mutant est muté au site de phosphorylation. Des cardiomyocytes en culture ont été infectés par les différents mutants en présence de leur activateur en amont ou de la β-galactosidase. Les réseaux d’α-actinine, ainsi que la taille des cardiomyocytes, ont été observés par microscopie. Les observations effectuées montrent que p38γ entraîne une désorganisation des réseaux d’α-actinine lorsqu’il est phosphorylé. Également, il facilite l’hypertrophie des cardiomyocytes en présence de son activateur s’il est forcé hors du noyau ou en l’absence de son motif de liaison aux domaines PDZ. En conclusion, les résultats obtenus suggèrent que p38γ exerce bel et bien un rôle dans le maintien structural des cardiomyocytes par l’intermédiaire de l’α-actinine.

Résumé: L’autophagie est un processus essentiel au maintien de l’homéostasie cellulaire. Elle permet de dégrader et recycler aussi bien des organelles entières que des composants cytoplasmiques non fonctionnels. De plus, l’augmentation d’autophagie en condition de stress constitue une réponse adaptative favorisant la survie cellulaire. Chez les cardiomyocytes, l’autophagie en condition basale est indispensable au renouvellement, entre autres, des mitochondries et des protéines formant les sarcomères. De plus, les stress tels l’ischémie cardiaque ou la carence en nutriments induisent une augmentation de l’autophagie protectrice. Dans certaines conditions extrêmes, il a été suggéré qu’un surcroît d’autophagie puisse toutefois exacerber la pathologie cardiaque en provoquant la mort des cardiomyocytes. Considérant l’importance de ce processus dans la physiopathologie cardiaque, l’identification des mécanismes signalétiques régulant l’autophagie chez les cardiomyocytes a été le sujet de recherches intenses. À cet effet, l’activation des Mitogen-Activated Protein Kinase (MAPK) a été démontrée pour réguler, avec d’autres voies signalétiques, l’autophagie et l’apoptose des cardiomyocytes. Il est donc probable que les Dual-Specificity Phosphatase (DUSP), enzymes clés contrôlant l’activité des MAPK, participent aussi à la régulation de l’autophagie. Afin de vérifier cette hypothèse, nous avons induit l’autophagie chez des cardiomyocytes isolés de rats nouveau-nés en culture. L’analyse de marqueurs d’autophagie par immunobuvardage démontre que l’activation des MAPK ERK1/2 et p38 corrèle avec l’activité autophagique chez les cardiomyocytes. Dans ces conditions, la diminution d’expression de la majorité des ARNm encodant les différentes DUSP retrouvées chez les cardiomyocytes contraste de façon marquée avec l’augmentation d’expression de l’ARNm Dusp5. De plus, nous avons démontré par une étude de gain de fonction que l’activation soutenue de p38 par surexpression d’un mutant MKK6 constitutivement actif stimule l’autophagie chez les cardiomyocytes. De façon surprenante, la perte de fonction de p38 obtenue par surexpression d’un mutant p38 dominant négatif n’altère en rien la réponse autophagique initiatrice dans notre modèle in vitro. Nos résultats suggèrent que les DUSP puissent réguler, via leurs actions sur les MAPK, d’importantes étapes du processus autophagique chez les cardiomyocytes. / Abstract: Autophagy is a process essential to the maintenance of cellular homeostasis. It helps degrade and recycle whole organelles and nonfunctional cytoplasmic components. In addition, the adaptative up regulation of autophagy in stress condition promotes cell survival. In cardiomyocytes basal autophagy is essential to the renewal of, among others, mitochondria and proteins forming sarcomeres. In addition, stresses such as ischemic heart or nutrient deficiency induce an increase in protective autophagy. In extreme conditions, it has been suggested that autophagy may exacerbate cardiac disease causing the death of cardiomyocytes. Considering the importance of this process in cardiac pathophysiology, identify ing safety mechanisms regulating autophagy in cardiomyocytes has been the subject of intense research. To this end, activation of mitogen-activated protein kinase (MAPK) has been demonstrated to regulate, with other signaling pathways, autophagy and cardiomyocyte apoptosis. It is therefore likely that Dual-Specificity Phosphatases (DUSPs), key enzymes that control the activity of MAPKs, also participate in the regulation of autophagy. To test this hypothesis, we have induced autophagy in isolated cardiomyocytes of newborn rats in culture. Analysis of autophagy markers by immunoblotting demonstrated that the activation of MAPKs ERK1/2 and p38 correlates with autophagic activity in cardiomyocytes. Under these conditions, the decrease in expression of the majority of mRNAs encoding different DUSPs found in cardiomyocytes contrast sharply with the increase mRNA expression of Dusp5. Furthermore, we demonstrated by again of function study that sustained activation of p38 by overexpression of a constitutively active MKK6 mutant stimulates autophagy in cardiomyocytes. Surprisingly, the loss of p38 function obtained by overexpression of a dominant negative p38 mutant does not affect the autophagic response in our in vitro model, but increases the lipidation of autophagosomes marker LC3. Our results suggest that DUSPs can regulate, through their actions on MAPKs, important stages of autophagy in cardiomyocytes.

Submitted by DHARA CARLESSO ZAMPIVA (dhara.zampiva@univates.br) on 2018-06-20T18:04:43Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) 2018StefaniStoll.pdf: 2349210 bytes, checksum: bf9fc66eaff3e59f76ec3d7a689383f6 (MD5) / Approved for entry into archive by Ana Paula Lisboa Monteiro (monteiro@univates.br) on 2018-06-22T20:30:00Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) 2018StefaniStoll.pdf: 2349210 bytes, checksum: bf9fc66eaff3e59f76ec3d7a689383f6 (MD5) / Made available in DSpace on 2018-06-22T20:30:00Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) 2018StefaniStoll.pdf: 2349210 bytes, checksum: bf9fc66eaff3e59f76ec3d7a689383f6 (MD5) Previous issue date: 2018-06-20 / CAPES / O câncer se trata de uma das principais causas de mortes no mundo, sendo o câncer de pulmão o primeiro em incidência mundial. No Brasil, o câncer de pulmão é o segundo principal responsável por mortes por câncer em homens (após câncer de próstata) e o quarto em mulheres - sendo o Rio Grande do Sul o segundo estado brasileiro com maior incidência de casos de câncer. Caracterizado pelo crescimento desordenado e desenfreado de células, o desenvolvimento tumoral é definido pela evasão da morte celular e tem sido intimamente correlacionado à inflamação. Tratamentos usuais do câncer, como quimioterapia e radioterapia, apresentam elevados efeitos adversos ao paciente, além do alto custo. Tendo em vista que a maior parte das drogas antineoplásicas produzidas são oriundas de compostos naturais ou de seus derivados, é constante a busca por novos metabólitos de origem natural, em especial os de origem vegetal - que apresentam potencial na busca por novas moléculas para síntese de fármacos. Diversos fitocomponentes, como o terpeno α-terpineol (TPN), apresentam efeito antiproliferativo e anticancerígeno em linhagens de adenocarcinoma de mama, próstata e ovário, e leucêmicas. Neste trabalho foi avaliado o potencial anti-proliferativo do TPN frente à seis linhagens tumorais humanas (A549, MCF-7, HT-29, Caco-2, LNCaP, ACP-03), sendo a A549 (câncer de pulmão) selecionada para experimentos de tratamento repetido por seis dias em associação com o quimioterápico doxorrubicina (DOXO). O mecanismo de morte celular, marcadores moleculares, atividade enzimática (JAK-3, JNK-3, p38-α), migração celular e inibição de TNF-α foram avaliados. Dentre as seis linhagens analisadas, três (A549, MCF-7, HT-29) apresentaram redução significativa da viabilidade celular após tratamento com o TPN por 48 h. A associação do TPN com a DOXO na linhagem A549 potencializou o efeito anti-proliferativo em comparação com a DOXO. Após seis dias de tratamento observou-se comportamento dose- e tempo-dependente da DOXO e do TPN sem apresentar diferença estatística entre eles. O TPN apresentou atividade inibitória da p38-α (IC50=729 μ M) e JAK3 (IC50=6,3 μM). Após 48 h de tratamento, observou-se e necrose nas células tratadas com DOXO (21,5 %) e TPN (7,3 %).Com a associação de ambas as drogas, a taxa de necrose elevou-se para 33,5 %, bem como para os seis dias de tratamento (52,3 %). Observou-se ainda, redução da migração celular após 120 h de tratamento com o TPN em comparação ao controle. Com base no exposto acima, o TPN apresenta potencial como biomolécula para o desenvolvimento de novos fármacos ou mesmo seu uso, como coadjuvante no tratamento de câncer de pulmão humano. / Cancer is one of the leading causes of death worldwide, with lung cancer as the major one. In Brazil, lung cancer is the second leading cause of cancer deaths in men (after the prostate cancer) and fourth in women. Rio Grande do Sul is the second Brazilian state with the highest incidence of cancer. Characterized by disordered cell growth, tumor development is defined by cell death evasion and has been closely correlated to inflammation. Standard cancer treatments, such as chemotherapy and radiotherapy, cause adverse effects on patients. Considering that most of the antineoplastic drugs produced are derived from natural compounds or their derivatives, natural products (especially those of plant origin) present potential in the search for new molecules for drug synthesis. Several phytoconstituents, such as the terpene α-terpineol (TPN), have antiproliferative and anticancer effects in cell lines of breast, prostate and ovary carcinomas, and leukemic cells. In the present study, the anti-proliferative potential of TPN on six human tumor cell lines (A549, MCF-7, HT-29, Caco-2, LNCaP and ACP-03) was evaluated. The A549 cell line (lung adenocarcinoma) was selected for experiments of six days with TPN and doxorubicin (DOXO) co-treatment. Mechanisms of cell death, molecular markers, enzymatic activity (JAK-3, JNK-3, p38-α), cell migration and inhibition of TNF-α were evaluated. Among the six lines, three of them (A549, MCF-7, HT-29) have shown a significant reduction of cell viability after 48 h treatment with TPN. Co-treatment of TPN and DOXO on A549 potentiated the antiproliferative effect compared with DOXO treatment. After six days of treatment, dose and time-dependent effect of DOXO and TPN were observed. TPN showed inhibitory activity on p38-α (IC50 = 729 μM) and JAK3 (IC50 = 6.3 μM). After 48 h of treatment, necrosis was observed in cells treated with DOXO (21,5 %) and TPN (7,3 %). The co-treatment of both drugs increased the necrosis rate up to 33,5 %, as well in the 6th day of treatment (52,3 %). It was also observed a cell migration reduction after 120 h of TPN treatment in comparison with control. Based on that, TPN can be characterized as a potential biomolecule for new drugs development or even its use as adjuvant in the treatment of lung adenocarcinoma.