TGFβ is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGFβ can suppress IgE-mediated mast cell activation in human and mouse mast cells in vitro. IL-33 is a recently discovered member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGFβ on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGFβ -1, -2, or -3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13 and MCP-1, in a concentration-dependent manner. Furthermore, TGFβ also reduced expression of the T1/ST2 receptor as well as IL-33-mediated TAK1 and ERK phosphorylation. TGF-ß1 injection suppressed IL-33-mediated production of systemic inflammatory cytokines in vivo. The role of IL-33 in the pathogenesis of allergic diseases is incompletely understood. These findings, consistent with our previously reported effects of TGFβ on IgE-mediated activation, demonstrate that TGFβ can provide broad and substantial inhibitory signals to activated mast cells.

Dynamics of acrosome reaction during intra-specific sperm competition in rodents Sperm acrosome integrity is disturbed in promiscuous species field mice (Apodemus) and more than half of the spermatozoa undergoing spontaneous acrosome reaction (AR) before binding to the zona pellucida. In Muridae it is documented a generally high rate of spontaneous AR, and the percentage increases in promiscuous species up to 60 % in 60 min capacitation in vitro. The acrosome integrity positively corellates with presence of CD46 protein which absence in wood mouse is fenotypicaly same as in CD46 knock-out mouse leading to accelerated spontaneous AR. It is necessary to clarify whether for mouse sperm it is essential the primary binding of intact sperm to zona pellucida of the egg or whether it is preferred secondary sperm binding after spontaneous AR. In this context, the question is whether there is a relocalization of the key fusion protein IZUMO in sperm during spontaneous AR. IZUMO relocalization was monitored by immunofluorescence at specific times of capacitation in vitro during spontaneous and induced AR. IZUMO relocalization as closely connected to actin cytoskeleton, and β1 integrins. Dynamics and localization of β1 integrin during spontaneous and induced AR was also detected by immunofluorescence. Our results...

Introdução: Proteínas da Superfamília do fator transformador de crescimento β (TGF-β) estão implicadas na regulação de diversas funções biológicas. Embora alguns estudos revelaram a sua presença no endométrio ectópico de portadoras de adenomiose, a sua função na etiopatogenia da doença permanece pouco conhecida. Objetivo: o estudo visa comparar a expressão imuno-histoquímica de TGF-β1 no endométrio ectópico de portadoras de adenomiose com o endométrio tópico de pacientes sem essa condição. Método: Estudo de caso-controle utilizando imuno-histoquímica em amostras uterinas (blocos de parafina) do Hospital de Clínicas de Porto Alegre. A amostra contém 28 casos de adenomiose e 21 controles. Resultados: Não encontramos associação entre tabagismo e adenomiose (P = 0,75), abortos e adenomiose (P = 0,29), gestações e adenomiose (P = 0,85), curetagens e adenomiose (P = 0,81), dor pélvica e adenomiose (P = 0,72) e presença de mioma e adenomiose (P = 0,15). Além disso encontramos relação entre sangramento uterino anormal (SUA) e adenomiose (P = 0,02) e cesarianas prévias e adenomiose (P = 0,02) . A expressão imuno-histoquímica de TGF-β1 no endométrio ectópico de portadoras de adenomiose não teve diferença significativa quando comparado com a expressão dessa proteína no endométrio tópico de pacientes sem adenomiose (P = 0,86). Conclusão: Nosso estudo foi um dos primeiros a comparar a expressão de TGF-β1 no endométrio de pacientes com e sem adenomiose. Em nossa análise não obtivemos diferença significativa entre os grupos, resultado diferente do encontrado em outros dois estudos. Mais estudos são necessários para investigar o papel da superfamília TGF no desenvolvimento e manutenção da adenomiose. / Background: Proteins of transforming growth factor β superfamily (TGF-β) are implicated in the regulation of various biological functions. Although some studies have revealed their presence in ectopic endometrium of women with adenomyosis, their role in the pathogenesis of the disease remains largely unknown. Objective: The study aims to compare the immunohistochemical expression of TGF- β1 in ectopic endometrium of women with adenomyosis with the topic endometrium of patients without this condition. Methods: Casecontrol study using immunohistochemistry in uterine samples (paraffin blocks) obteined from Hospital de Clínicas de Porto Alegre. The sample contained 28 adenomyosis cases and 21 controls. Results: We found no significant difference between smoking and adenomyosis (P = 0.75), abortions and adenomyosis (P = 0.29), pregnancies and adenomyosis (P = 0.85), curettage and adenomyosis (P = 0.81), pelvic pain and adenomyosis (P = 0.72) and presence of myoma and adenomyosis (P = 0.15). We did find a relationship between adenomyosis and abnormal uterine bleeding (AUB) (P = 0.02) and previous cesarean section and adenomyosis (P = 0.02). Immunohistochemical expression of TGF-β1 in ectopic endometrium of women with adenomyosis did not have significant difference when compared with the expression of this protein in the topic endometrium of patients without adenomyosis (P = 0.86). Conclusion: Our study was one of the first to compare the TGF-β1 expression in the endometrium of patients with and without adenomyosis. In our analysis we have not had significant difference between the groups, unlike observed in two other studies. More studies are needed to investigate the role of TGF superfamily in the development and maintenance of adenomyosis.

<p>Integrins are heterodimeric cell surface receptors, composed of an α and a β subunit, mainly binding for extracellular matrix proteins. lntegrin subunit β1 can combine with at least 12 a subunits and thus form the biggest subfamily within the integrin family. In this thesis, functional properties of the splice variant β1Β, and the effects of several mutations in the cytoplasmic tail of integrin subunit β1Α were studied. In addition, the border between the transmembrane and cytoplasmic domains of several integrin subunits was determined.</p><p>The β1Β splice variant has been reported to have a dominant negative effect on functions of β1Α integrins. In this study, it was studied if the expression of β1Β had similar negative effects on the αvβ3 integrin functions since the β3 subunit is structurally similar to β1Α. The β1Β subunit was expressed in an integrin β1-deficient cell line and it was found that the presence of β1Β does not interfere with adhesion or signaling of endogenous αvβ3</p><p>The border between the cytoplasmic domain and the C-terminal end of the transmembrane domain of integrin α and β subunits has been unclear. This question was experimentally addressed for integrin subunits β1, β2, α2 and α5. It was found that integrin subunits contain a positively charged lysine, which is embedded in the membrane in the absence of interacting proteins.</p><p>The functional importance of the lysine in integrin transmembrane domains was investigated by mutating this amino acid to leucine in β1Α. The mutation affected cell spreading and tyrosine phosphorylation of the adapter protein CAS. The activation of focal adhesion kinase and tyrosine phosphorylation of paxillin was not affected. Furthermore, the mutation of two tyrosines to phenylalanines in the β1Α cytoplasmic tail was found to reduce the capability of β1Α integrins to mediate cell spreading and migration. Activation of focal adhesion kinase in response to the later β1Α mutant was shown to be impaired as well as tyrosine phosphorylation of adapter proteins paxillin and tensin whereas overall tyrosine phosphorylation of CAS was unaffected. These data suggests the presence of focal adhesion kinase-dependent and -independent pathways for tyrosine phosphorylation of CAS after integrin β1Α-mediated adhesion. </p>

Integrins are heterodimeric cell surface receptors, composed of an α and a β subunit, mainly binding for extracellular matrix proteins. lntegrin subunit β1 can combine with at least 12 a subunits and thus form the biggest subfamily within the integrin family. In this thesis, functional properties of the splice variant β1Β, and the effects of several mutations in the cytoplasmic tail of integrin subunit β1Α were studied. In addition, the border between the transmembrane and cytoplasmic domains of several integrin subunits was determined. The β1Β splice variant has been reported to have a dominant negative effect on functions of β1Α integrins. In this study, it was studied if the expression of β1Β had similar negative effects on the αvβ3 integrin functions since the β3 subunit is structurally similar to β1Α. The β1Β subunit was expressed in an integrin β1-deficient cell line and it was found that the presence of β1Β does not interfere with adhesion or signaling of endogenous αvβ3 The border between the cytoplasmic domain and the C-terminal end of the transmembrane domain of integrin α and β subunits has been unclear. This question was experimentally addressed for integrin subunits β1, β2, α2 and α5. It was found that integrin subunits contain a positively charged lysine, which is embedded in the membrane in the absence of interacting proteins. The functional importance of the lysine in integrin transmembrane domains was investigated by mutating this amino acid to leucine in β1Α. The mutation affected cell spreading and tyrosine phosphorylation of the adapter protein CAS. The activation of focal adhesion kinase and tyrosine phosphorylation of paxillin was not affected. Furthermore, the mutation of two tyrosines to phenylalanines in the β1Α cytoplasmic tail was found to reduce the capability of β1Α integrins to mediate cell spreading and migration. Activation of focal adhesion kinase in response to the later β1Α mutant was shown to be impaired as well as tyrosine phosphorylation of adapter proteins paxillin and tensin whereas overall tyrosine phosphorylation of CAS was unaffected. These data suggests the presence of focal adhesion kinase-dependent and -independent pathways for tyrosine phosphorylation of CAS after integrin β1Α-mediated adhesion.

myo-lnositol (mIns), a natural component of the human diet and essential precursor of several signalling pathways, including that of G protein-coupled receptors, has also been shown to be effective in the treatment of psychiatric disorders such as depression, obsessive compulsive disorder and panic disorder. Most likely since mlns is a simple isomer of glucose, no serious side effects have been reported with its use, even at high oral doses of mlns. Previous studies suggest that the therapeutic action of mlns may include reduced serotonin 5HTzA and muscarinic acetylcholine receptor function. An important signal transduction system that may possibly be involved in the mechanism of action of antidepressants is phosphoinositide (PI) turnover. In this signalling system PI-phospholipase C (PLCpl), that is implicated in the in the mechanism of action of antidepressants and anxiolytics, is activated. The mechanism of action of mlns, however, still remains elusive and needs further investigation. In this study a possible modulatory role of 24-hour pre-treatment of human neuroblastoma cell line (SH-SY5Y) with mlns on mRNA levels and protein expression of phospholipase C-p1 (PLCP1) and glycogen synthase kinase 3P (GSK3p) was investigated. The effects of mlns were also compared to that of other prototype antidepressants, such as fluoxetine (a selective serotonin reuptake inhibitor), imipramine (a tricyclic antidepressant), lithium and another drug with potential antidepressant effects, sildenafil (phosphodiesterase 5-type (PDE5) inhibitor). Real-time reverse transcription Polymerase Chain Reaction (RTPCR) was performed in order to investigate the mRNA levels, while protein expression in membranes and the cytosol fraction of cells were quantified with Western blots. The expression of PLCPl was decreased after pre-treatments with imipramine or myoinositol in combination with fluoxetine. In addition, sildenafil alone or in combination with myo-inositol, also decreased the expression of membrane-bound PLCp1. However, a 24- hour pre-treatment with lithium did not alter PLCPl expression significantly. Determined mRNA levels for the expression of PLCPl were consistent in these findings, except for the inhibition of the mRNA for the expression of PLCPl also after lithium treatment. The reduced PLCpl mRNA levels after lithium pre-treatment may suggest the involvement of posttranscriptional modification (or delayed translational effects) of PLCpl after lithium treatment. The data from the current study suggest that antidepressant action may include downregulation of PLCPl expression and that modulators of the nitric oxidecGMP pathway (e.g. sildenafil as a PDE5 inhibitor) may exhibit similar properties. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.

myo-lnositol (mIns), a natural component of the human diet and essential precursor of several signalling pathways, including that of G protein-coupled receptors, has also been shown to be effective in the treatment of psychiatric disorders such as depression, obsessive compulsive disorder and panic disorder. Most likely since mlns is a simple isomer of glucose, no serious side effects have been reported with its use, even at high oral doses of mlns. Previous studies suggest that the therapeutic action of mlns may include reduced serotonin 5HTzA and muscarinic acetylcholine receptor function. An important signal transduction system that may possibly be involved in the mechanism of action of antidepressants is phosphoinositide (PI) turnover. In this signalling system PI-phospholipase C (PLCpl), that is implicated in the in the mechanism of action of antidepressants and anxiolytics, is activated. The mechanism of action of mlns, however, still remains elusive and needs further investigation. In this study a possible modulatory role of 24-hour pre-treatment of human neuroblastoma cell line (SH-SY5Y) with mlns on mRNA levels and protein expression of phospholipase C-p1 (PLCP1) and glycogen synthase kinase 3P (GSK3p) was investigated. The effects of mlns were also compared to that of other prototype antidepressants, such as fluoxetine (a selective serotonin reuptake inhibitor), imipramine (a tricyclic antidepressant), lithium and another drug with potential antidepressant effects, sildenafil (phosphodiesterase 5-type (PDE5) inhibitor). Real-time reverse transcription Polymerase Chain Reaction (RTPCR) was performed in order to investigate the mRNA levels, while protein expression in membranes and the cytosol fraction of cells were quantified with Western blots. The expression of PLCPl was decreased after pre-treatments with imipramine or myoinositol in combination with fluoxetine. In addition, sildenafil alone or in combination with myo-inositol, also decreased the expression of membrane-bound PLCp1. However, a 24- hour pre-treatment with lithium did not alter PLCPl expression significantly. Determined mRNA levels for the expression of PLCPl were consistent in these findings, except for the inhibition of the mRNA for the expression of PLCPl also after lithium treatment. The reduced PLCpl mRNA levels after lithium pre-treatment may suggest the involvement of posttranscriptional modification (or delayed translational effects) of PLCpl after lithium treatment. The data from the current study suggest that antidepressant action may include downregulation of PLCPl expression and that modulators of the nitric oxidecGMP pathway (e.g. sildenafil as a PDE5 inhibitor) may exhibit similar properties. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.

Introdução: Proteínas da Superfamília do fator transformador de crescimento β (TGF-β) estão implicadas na regulação de diversas funções biológicas. Embora alguns estudos revelaram a sua presença no endométrio ectópico de portadoras de adenomiose, a sua função na etiopatogenia da doença permanece pouco conhecida. Objetivo: o estudo visa comparar a expressão imuno-histoquímica de TGF-β1 no endométrio ectópico de portadoras de adenomiose com o endométrio tópico de pacientes sem essa condição. Método: Estudo de caso-controle utilizando imuno-histoquímica em amostras uterinas (blocos de parafina) do Hospital de Clínicas de Porto Alegre. A amostra contém 28 casos de adenomiose e 21 controles. Resultados: Não encontramos associação entre tabagismo e adenomiose (P = 0,75), abortos e adenomiose (P = 0,29), gestações e adenomiose (P = 0,85), curetagens e adenomiose (P = 0,81), dor pélvica e adenomiose (P = 0,72) e presença de mioma e adenomiose (P = 0,15). Além disso encontramos relação entre sangramento uterino anormal (SUA) e adenomiose (P = 0,02) e cesarianas prévias e adenomiose (P = 0,02) . A expressão imuno-histoquímica de TGF-β1 no endométrio ectópico de portadoras de adenomiose não teve diferença significativa quando comparado com a expressão dessa proteína no endométrio tópico de pacientes sem adenomiose (P = 0,86). Conclusão: Nosso estudo foi um dos primeiros a comparar a expressão de TGF-β1 no endométrio de pacientes com e sem adenomiose. Em nossa análise não obtivemos diferença significativa entre os grupos, resultado diferente do encontrado em outros dois estudos. Mais estudos são necessários para investigar o papel da superfamília TGF no desenvolvimento e manutenção da adenomiose. / Background: Proteins of transforming growth factor β superfamily (TGF-β) are implicated in the regulation of various biological functions. Although some studies have revealed their presence in ectopic endometrium of women with adenomyosis, their role in the pathogenesis of the disease remains largely unknown. Objective: The study aims to compare the immunohistochemical expression of TGF- β1 in ectopic endometrium of women with adenomyosis with the topic endometrium of patients without this condition. Methods: Casecontrol study using immunohistochemistry in uterine samples (paraffin blocks) obteined from Hospital de Clínicas de Porto Alegre. The sample contained 28 adenomyosis cases and 21 controls. Results: We found no significant difference between smoking and adenomyosis (P = 0.75), abortions and adenomyosis (P = 0.29), pregnancies and adenomyosis (P = 0.85), curettage and adenomyosis (P = 0.81), pelvic pain and adenomyosis (P = 0.72) and presence of myoma and adenomyosis (P = 0.15). We did find a relationship between adenomyosis and abnormal uterine bleeding (AUB) (P = 0.02) and previous cesarean section and adenomyosis (P = 0.02). Immunohistochemical expression of TGF-β1 in ectopic endometrium of women with adenomyosis did not have significant difference when compared with the expression of this protein in the topic endometrium of patients without adenomyosis (P = 0.86). Conclusion: Our study was one of the first to compare the TGF-β1 expression in the endometrium of patients with and without adenomyosis. In our analysis we have not had significant difference between the groups, unlike observed in two other studies. More studies are needed to investigate the role of TGF superfamily in the development and maintenance of adenomyosis.

Introdução: Proteínas da Superfamília do fator transformador de crescimento β (TGF-β) estão implicadas na regulação de diversas funções biológicas. Embora alguns estudos revelaram a sua presença no endométrio ectópico de portadoras de adenomiose, a sua função na etiopatogenia da doença permanece pouco conhecida. Objetivo: o estudo visa comparar a expressão imuno-histoquímica de TGF-β1 no endométrio ectópico de portadoras de adenomiose com o endométrio tópico de pacientes sem essa condição. Método: Estudo de caso-controle utilizando imuno-histoquímica em amostras uterinas (blocos de parafina) do Hospital de Clínicas de Porto Alegre. A amostra contém 28 casos de adenomiose e 21 controles. Resultados: Não encontramos associação entre tabagismo e adenomiose (P = 0,75), abortos e adenomiose (P = 0,29), gestações e adenomiose (P = 0,85), curetagens e adenomiose (P = 0,81), dor pélvica e adenomiose (P = 0,72) e presença de mioma e adenomiose (P = 0,15). Além disso encontramos relação entre sangramento uterino anormal (SUA) e adenomiose (P = 0,02) e cesarianas prévias e adenomiose (P = 0,02) . A expressão imuno-histoquímica de TGF-β1 no endométrio ectópico de portadoras de adenomiose não teve diferença significativa quando comparado com a expressão dessa proteína no endométrio tópico de pacientes sem adenomiose (P = 0,86). Conclusão: Nosso estudo foi um dos primeiros a comparar a expressão de TGF-β1 no endométrio de pacientes com e sem adenomiose. Em nossa análise não obtivemos diferença significativa entre os grupos, resultado diferente do encontrado em outros dois estudos. Mais estudos são necessários para investigar o papel da superfamília TGF no desenvolvimento e manutenção da adenomiose. / Background: Proteins of transforming growth factor β superfamily (TGF-β) are implicated in the regulation of various biological functions. Although some studies have revealed their presence in ectopic endometrium of women with adenomyosis, their role in the pathogenesis of the disease remains largely unknown. Objective: The study aims to compare the immunohistochemical expression of TGF- β1 in ectopic endometrium of women with adenomyosis with the topic endometrium of patients without this condition. Methods: Casecontrol study using immunohistochemistry in uterine samples (paraffin blocks) obteined from Hospital de Clínicas de Porto Alegre. The sample contained 28 adenomyosis cases and 21 controls. Results: We found no significant difference between smoking and adenomyosis (P = 0.75), abortions and adenomyosis (P = 0.29), pregnancies and adenomyosis (P = 0.85), curettage and adenomyosis (P = 0.81), pelvic pain and adenomyosis (P = 0.72) and presence of myoma and adenomyosis (P = 0.15). We did find a relationship between adenomyosis and abnormal uterine bleeding (AUB) (P = 0.02) and previous cesarean section and adenomyosis (P = 0.02). Immunohistochemical expression of TGF-β1 in ectopic endometrium of women with adenomyosis did not have significant difference when compared with the expression of this protein in the topic endometrium of patients without adenomyosis (P = 0.86). Conclusion: Our study was one of the first to compare the TGF-β1 expression in the endometrium of patients with and without adenomyosis. In our analysis we have not had significant difference between the groups, unlike observed in two other studies. More studies are needed to investigate the role of TGF superfamily in the development and maintenance of adenomyosis.

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No. of bitstreams: 1 erickestevesdeoliveira.pdf: 1235775 bytes, checksum: d5513847048574c1ada373c0b486b859 (MD5) Previous issue date: 2015-02-24 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Ocimum. gratissimum L. e Mentha x villosa Huds. são duas plantas aromáticas que são amplamente utilizadas no Brasil e em outros países tanto para fins terapêuticos, como na culinária. Diversas atividades farmacológicas já foram descritas para essas duas plantas e para os componentes majoritários de seus óleos essenciais, Eugenol e Óxido de Piperitenona, respectivamente. Porém ainda há a carência de estudos sobre a atividade antiproliferativa desses óleos essenciais sobre linhagens tumorais e as implicações desses compostos sobre a produção de TGF-1, uma citocina que, em tumores já estabelecidos, apresenta efeito pró-tumoral. Esse estudo visa avaliar os efeitos dos tratamentos com os óleos essenciais de O. gratissimum e M. x villosa, sobre uma linhagem de adenocarcinoma humano de pulmão produtora de TGF-1. Métodos: A viabilidade celular foi avaliada através do ensaio de MTT em linhagens de células (A549 e J774 A.1) e em macrófagos intraperitoneais tratados com 5 a 200g/mL, por 48h. O efeito dos óleos essenciais sobre o ciclo celular foi avaliado através de marcação com iodeto de propídio e quantificação das fases de ciclo celular por citometria de fluxo. A quantificação de células em SubG1 foi utilizada como parâmetro para avaliação de apoptose, que foi confirmada através da marcação de TUNEL. A produção de TGF-1 foi avaliada por ELISA. Resultados: Os dois óleos essenciais reduziram a viabilidade da linhagem celular A549 (IC50: OG:160g/mL / MV:117g/mL), os tratamentos também induziram parada do ciclo celular em S com 24h de tratamento (controle: 12,31±0,89 / OEOG: 15,70±1,15 / OEMV: 23,35±0,75) efeito já registrado para eugenol. Também houve aumento do percentual de células em SubG1 (controle: 15,05±0,71 / OEOG: 91,94±1,71 / OEMV:24,62±1,06), indicando aumento da fragmentação de DNA, um dos sinais de apoptose, que foi confirmado pelo aumento da mediana de fluorescência na marcação de TUNEL (controle:59.1±3.4 / OEOG:68.6±3.7 / OEMV:75.3±15.7). Houve redução da produção de TGF-1 nas concentrações não letais dos óleos essenciais (10 e 50g/mL). Conclusões: Esses dados demonstram o potencial indutor de apoptose e de parada de ciclo celular, desses óleos essenciais para o tratamento de tumores, sobretudo aqueles caracterizados pela produção de TGF-1, citocina importante para a sobrevivência e proliferação de células tumorais. Contudo, essa citocina desempenha papéis importantes na homeostase do organismo, e por isso são necessários estudos que avaliem o efeito sistêmico desses óleos essenciais. / Ocimum. gratissimum L. and Mentha x villosa Huds are aromatic plants largely used, in Brazil and other countries, for therapeutic and culinary purposes. Several pharmacological properties have been described for their essential oil and their major compounds: Eugenol and piperitenone oxide respectively. However, the antiproliferative effect and the blockage of the TGF-1 production are poorly understood. This cytokine contributes for the development of late-phase tumors. This study aimed to evaluate the effects of the essential oils of Ocimum gratissimum and Mentha x villosa over a TGF-1 producer human lung adenocarcinoma cell line. Methodology: Viability was assessed through MTT assay, on cell lineages (A549 and J774 A.1) and intraperitoneal macrophages treated for 48h with essential oil concentrations ranging from 5 to 200g/mL. Cell cycle and SubG1 DNA amount was evaluated through propidium iodide staining followed by flow citometry analysis. TUNEL assay was used to quantify the DNA fragmentation. ELISA was performed to measure the TGF-1 production. Results: Both essential oils reduced A549 cell viability (IC50: EOOG:160g/mL / EOMV:117g/mL), there was also cell cycle arrest at S phase, after 24hours of treatment (control: 12,31±0,89 / EOOG: 15,70±1,15 / EOMV: 23,35±0,75). SubG1 DNA amount was also elevated after treatment (control: 15,05±0,71 / EOOG: 91,94±1,71 / EOMV:24,62±1,06), an indicative of DNA fragmentation, one of the apoptosis sign. This effect was confirmed by the elevated TUNEL labeling. The non-lethal concentrations of the essential oils (10 and 50g/mL) led to the reduction of TGF-1 production. Conclusion: These data indicates the apoptotic and cell cycle arrest effects of the essential oils, mainly over TGF-1 producing tumors. As this cytokine has a key role over the survival and proliferation of these cancer cells. The possible systemic effects of these treatments are yet to be evaluated, as the TGF-1 blockage may affect the maintenance of homeostasis.