RESUMO
The goal of this research was to explore the preliminary anticancer properties of five plants namely Calotropis procera, Moringa oleifera, Millettia pinnata, Basela alba and Euphorbia neriifolia available in Jharkhand which is used for the medicinal purpose by local tribes. In the present study, plant leaves from five species were collected, dried and extracted with solvents of increasing polarity, followed by assessment of their cytotoxicity in A549 non-small-cell lung cancer cells. In the antimicrobial assay, the methanol extract of the M. pinnata leaves exhibited comparatively higher zone of inhibition of 0.7 ± 0.20 cm against a Salmonella typhi culture than the other extracts. M. pinnata leaves extract also displayed the maximum percentage inhibition in the DPPH, 83.97 ± 0.01 FRAP, 193.14 ± 3.01 mM assays. Furthermore, the cytotoxicity of the chloroform (37.45 ± 1.04) and ethyl acetate extracts (34.20 ± 0.81) of M. pinnata against A549 cells was found relatively higher with respect to another extract. In contrast, a study with the L132 normal epithelial lung cell line revealed less toxicity from the chloroform extract (0.33 ± 0.19) compared to the ethyl acetate extract (6.65 ± 0.59). Based on these findings, phytochemical investigation on chloroform and ethyl acetate extract of M. pinnata was performed using UPLC-ESI-MS/MS analysis revealing the presence of ß-sitosterol, lanceolatin B, karanjin, and stigmasterol. Congruently, a complete phytochemical and cytotoxic investigation of the M. pinnata extract constituents might infer the potency of this extract/s as anticancer, antioxidant and antimicrobial agents.
RESUMO
The pressing need for new pest control products with novel modes of action has spawned interest in small molecules and peptides targeting arthropod GPCRs. Genome sequence data and tools for reverse genetics have enabled the prediction and characterization of GPCRs from many invertebrates. We review recent work to identify, characterize and de-orphanize arthropod GPCRs, with a focus on studies that reveal exciting new functional roles for these receptors, including the regulation of metabolic resistance. We explore the potential for insecticides targeting Class A biogenic amine-binding and peptide-binding receptors, and consider the innovation required to generate pest-selective leads for development, within the context of new PCR-targeting products to control arthropod vectors of disease.
Assuntos
Genômica/métodos , Controle de Insetos/métodos , Insetos Vetores/genética , Insetos/genética , Inseticidas/farmacologia , Receptores Acoplados a Proteínas G/genética , Animais , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMO
Female Aedes aegypti mosquitoes infect more than 400 million people each year with dangerous viral pathogens including dengue, yellow fever, Zika and chikungunya. Progress in understanding the biology of mosquitoes and developing the tools to fight them has been slowed by the lack of a high-quality genome assembly. Here we combine diverse technologies to produce the markedly improved, fully re-annotated AaegL5 genome assembly, and demonstrate how it accelerates mosquito science. We anchored physical and cytogenetic maps, doubled the number of known chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites, provided further insight into the size and composition of the sex-determining M locus, and revealed copy-number variation among glutathione S-transferase genes that are important for insecticide resistance. Using high-resolution quantitative trait locus and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly disease vector.
Assuntos
Aedes/genética , Infecções por Arbovirus/virologia , Arbovírus , Genoma de Inseto/genética , Genômica/normas , Controle de Insetos , Mosquitos Vetores/genética , Mosquitos Vetores/virologia , Aedes/virologia , Animais , Infecções por Arbovirus/transmissão , Arbovírus/isolamento & purificação , Variações do Número de Cópias de DNA/genética , Vírus da Dengue/isolamento & purificação , Feminino , Variação Genética/genética , Genética Populacional , Glutationa Transferase/genética , Resistência a Inseticidas/efeitos dos fármacos , Masculino , Anotação de Sequência Molecular , Família Multigênica/genética , Piretrinas/farmacologia , Padrões de Referência , Processos de Determinação Sexual/genéticaRESUMO
In order to promote the natural healing process, drug-functionalized nanofibrous transdermal substitute was fabricated using gellan as chief polymer and polyvinyl alcohol (PVA) as supporting polymer via electrospinning technique. These fabricated nanofibers physiochemically mimic the extracellular matrix (ECM) which supports the cell growth. For neo-tissue regeneration in a sterilized environment, amoxicillin (Amx) was entrapped within these nanofibers. Entrapment of Amx in the nanofibers was confirmed by FESEM, FTIR, XRD and TG analysis. In vitro cell culture studies revealed that the fabricated non-cytotoxic nanofibers promoted enhance cell adherence and proliferation of human keratinocytes. A preliminary in vivo study performed on rat model for full thickness skin excision wound demonstrated the prompt re-epithelialization in early phase and quicker collagen deposition in later phases of wound healing in case of Amx-functionalized gellan/PVA nanofibers. Data collectively confirmed the potential usage of gellan based electrospun nanofibers as transdermal substitute for faster skin restoration.
Assuntos
Nanofibras , Álcool de Polivinil , Cicatrização , Administração Cutânea , Animais , Colágeno , Humanos , Ratos , Regeneração , Fenômenos Fisiológicos da Pele , Alicerces TeciduaisRESUMO
Angiogenesis plays important roles in tumor growth and metastasis, thus development of a novel angiogenesis inhibitor is essential for the improvement of therapeutics against cancer. Thrombospondins-1 (TSP-1) is a potent endogenous inhibitor of angiogenesis that acts through direct effects on endothelial cell migration, proliferation, survival, and activating apoptotic pathways. TSP-1 has been shown to disrupt estrogen-induced endothelial cell proliferation and migration. Here we investigated the potential of pterostilbene carboxaldehyde thiosemicarbazone (PTERC-T), a novel resveratrol (RESV) derivative, to inhibit angiogenesis induced by female sex steroids, particularly 17ß-Estradiol (E2), on Human umbilical vein endothelial cells (HUVECs) and to elucidate the involvement of TSP-1 in PTERC-T action. Our results showed that PTERC-T significantly inhibited 17ß-E2-stimulated proliferation of HUVECs and induced apoptosis as determined by annexin V/propidium iodide staining and cleaved caspase-3 expression. Furthermore, PTERC-T also inhibited endothelial cell migration, and invasion in chick chorioallantoic membrane (CAM) assay. In contrast, RESV failed to inhibit 17ß-E2 induced HUVECs proliferation and invasion at similar dose. PTERC-T was also found to increase TSP-1 protein expression levels in a dose-dependent manner which, however, was counteracted by co-incubation with p38MAPK or JNK inhibitors, suggesting involvement of these pathways in PTERC-T action. These results suggest that the inhibitory effect of PTERC-T on 17ß-E2 induced angiogenesis is associated, at least in part, with its induction of endothelial cell apoptosis and inhibition of cell migration through targeting TSP-1. Thus, PTERC-T could be considered as a potential lead compound for developing a class of new drugs targeting angiogenesis-related diseases.
Assuntos
Movimento Celular/efeitos dos fármacos , Estradiol/farmacologia , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Estilbenos/química , Estilbenos/farmacologia , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Receptores de Estrogênio/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Resveratrol , Trombospondina 1/genética , Regulação para Cima/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: A dysfunctional osteoclast activity is often the cause of bone destructive diseases, such as osteoporosis, periodontitis, erosive arthritis, and cancer. The NFκB ligand (RANKL) has been identified as a major mediator of bone resorption. Agents that suppress RANKL signaling have the potential to inhibit bone resorption or osteoclastogenesis. The present study aimed to determine the effect of a pterostilbene derivative (PTERC-T) for suppressing RANKL or tumor cells-induced osteoclastogenesis in RAW264.7 murine macrophages. METHODS: Cytotoxicity was measured by MTT assay and inhibitory effect on osteoclastogenesis was analyzed by counting the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and measuring the expression levels of the osteoclast-specific genes. The reactive oxygen species (ROS) generation was detected by FACS. Further, signaling pathways were analyzed by immunofluorescence and immunoblot analyses. RESULTS: PTERC-T suppressed the differentiation of monocytes to osteoclasts in a dose and time-dependent manner. The expression of osteoclast marker genes like TRAP, cathepsin K (CTSK), matrix metalloproteinase 9 (MMP9) and transcription factors c-Fos, and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) were also diminished by PTERC-T. PTERC-T scavenged intracellular ROS generation within osteoclast precursors during RANKL-stimulated osteoclastogenesis. Mechanistically, PTERC-T abrogated the phosphorylation of MAPKs (ERK and JNK) and inhibited RANKL-induced activation of NFκB by suppressing IκBα phosphorylation and preventing NFκB/p65 nuclear translocation. CONCLUSIONS: This study thus identifies PTERC-T as an inhibitor of osteoclast formation and provides evidence for its role in preventing osteoporosis and other bone related disorders. However, further studies are needed to establish its efficacy in vivo.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Ligante RANK/metabolismo , Estilbenos/química , Tiossemicarbazonas/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ligante RANK/antagonistas & inibidores , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Estilbenos/farmacologia , Fatores de Transcrição/metabolismoRESUMO
Inflammatory response plays an important role not only in the normal physiology, but also in the pathology of certain diseases such as cancers. In our previous study, we found a novel derivative of pterostilbene (PTER), to be an effective inducer of apoptosis in human breast and prostate cancer cells affecting various cellular targets. Herein, we further attempted to investigate its anti-inflammatory potential followed by its probable mode of action. The newly developed compound was tested for its anti-inflammatory actions in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages and carrageenan induced rat paw edema models. Our data showed that the derivative inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the downstream products like nitric oxide (NO) and PGE2, at much lower doses as compared to PTER. This effect was found to be associated with the inhibition of phosphorylation/degradation of IκB-α and nuclear translocation of the p-NFκB p65. Moreover, inhibition of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) was also observed. In addition, the newly developed compound also reduced the paw edema, the tissue content of NO, PGE2 and expression of iNOS and COX-2 proteins within the tissues after λ-carrageenan stimulation. Taken together, our findings provide the possibility that the PTER derivative might have enhanced cancer chemopreventive potential based on its stronger anti-NFκB and anti-inflammatory activities as compared to its natural counterpart, i.e., PTER. Thus, this compound can be used towards the development of an effective anti-inflammatory agent.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Estilbenos/farmacologia , Animais , Antioxidantes/farmacologia , Carragenina , Ciclo-Oxigenase 2/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Pé/patologia , Proteínas I-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Ratos , Fator de Transcrição AP-1/genética , Fator de Transcrição RelA/efeitos dos fármacos , Fator de Transcrição RelA/metabolismoRESUMO
Triorganotins, such as tributyltin chloride (TBTCl), are environmental contaminants that are commonly found in the antifouling paints used in ships and other vessels. The importance of TBTCl as an endocrine-disrupting chemical (EDC) in different animal models is well known; however, its adverse effects on the thyroid gland are less understood. Hence, in the present study, we aimed to evaluate the thyroid-disrupting effects of this chemical using both in vitro and in vivo approaches. We used HepG2 hepatocarcinoma cells for the in vitro studies, as they are a thyroid hormone receptor (TR)-positive and thyroid responsive cell line. For the in vivo studies, Swiss albino male mice were exposed to three doses of TBTCl (0.5, 5 and 50µg/kg/day) for 45days. TBTCl showed a hypo-thyroidal effect in vivo. Low-dose treatment of TBTCl exposure markedly decreased the serum thyroid hormone levels via the down-regulation of the thyroid peroxidase (TPO) and thyroglobulin (Tg) genes by 40% and 25%, respectively, while augmenting the thyroid stimulating hormone (TSH) levels. Thyroid-stimulating hormone receptor (TSHR) expression was up-regulated in the thyroid glands of treated mice by 6.6-fold relative to vehicle-treated mice (p<0.05). In the transient transactivation assays, TBTCl suppressed T3 mediated transcriptional activity in a dose-dependent manner. In addition, TBTCl was found to decrease the expression of TR. The present study thus indicates that low concentrations of TBTCl suppress TR transcription by disrupting the physiological concentrations of T3/T4, followed by the recruitment of NCoR to TR, providing a novel insight into the thyroid hormone-disrupting effects of this chemical.
Assuntos
Disruptores Endócrinos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Receptores dos Hormônios Tireóideos/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo , Compostos de Trialquitina/farmacologia , Animais , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Técnicas In Vitro , Iodeto Peroxidase/genética , Iodeto Peroxidase/metabolismo , Masculino , Camundongos , Receptores dos Hormônios Tireóideos/genética , Glândula Tireoide/efeitos dos fármacos , Compostos de Trialquitina/administração & dosagemRESUMO
Trans-3,5-dimethoxy-4'-hydroxystilbene (PTER), a natural dimethylated analog of resveratrol, preferentially induces certain cancer cells to undergo apoptosis and could thus have a role in cancer chemoprevention. Peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, is a ligand-dependent transcription factor whose activation results in growth arrest and/or apoptosis in a variety of cancer cells. Here we investigated the potential of PTER-isothiocyanate (ITC) conjugate, a novel class of hybrid compound (PTER-ITC) synthesized by appending an ITC moiety to the PTER backbone, to induce apoptotic cell death in hormone-dependent (MCF-7) and -independent (MDA-MB-231) breast cancer cell lines and to elucidate PPARγ involvement in PTER-ITC action. Our results showed that when pre-treated with PPARγ antagonists or PPARγ siRNA, both breast cancer cell lines suppressed PTER-ITC-induced apoptosis, as determined by annexin V/propidium iodide staining and cleaved caspase-9 expression. Furthermore, PTER-ITC significantly increased PPARγ mRNA and protein levels in a dose-dependent manner and modulated expression of PPARγ-related genes in both breast cancer cell lines. This increase in PPARγ activity was prevented by a PPARγ-specific inhibitor, in support of our hypothesis that PTER-ITC can act as a PPARγ activator. PTER-ITC-mediated upregulation of PPARγ was counteracted by co-incubation with p38 MAPK or JNK inhibitors, suggesting involvement of these pathways in PTER-ITC action. Molecular docking analysis further suggested that PTER-ITC interacted with 5 polar and 8 non-polar residues within the PPARγ ligand-binding pocket, which are reported to be critical for its activity. Collectively, our observations suggest potential applications for PTER-ITC in breast cancer prevention and treatment through modulation of the PPARγ activation pathway.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , PPAR gama/metabolismo , Análise de Variância , Anexina A5 , Antineoplásicos/metabolismo , Compostos Azo , Western Blotting , Caspase 9/metabolismo , Primers do DNA/genética , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Isotiocianatos/química , Isotiocianatos/farmacologia , Luciferases , Células MCF-7 , Estrutura Molecular , PPAR gama/antagonistas & inibidores , Propídio , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estilbenos/química , Estilbenos/farmacologiaRESUMO
Phthalates are the diverse group of compounds abundantly present in environment. The present study shows the estrogenic potential of diethyl phthalate (DEP). The data showed that DEP increased the transactivation of ER in CHO and MCF-7 cells suggesting its interaction with ER. In vivo parameters like increased uterine epithelial cell height and up regulation of various steroidogenic genes were also observed in adult female rats. Our uterotrophic assay data from immature female rats suggested that DEP treatment resulted in augmentation of uterine weight as well as luminal epithelial cell heights in both vaginal and uterine tissues. Further, DEP was able to upregulate pS2 gene expression with simultaneous activation of MAPK pathway as demonstrated by increased p-ERK/ERK ratio. Taken together, the present data suggests that DEP acts as an estrogenic compound and based on these data further detailed studies would reveal its mode of action at cellular levels.
Assuntos
Ácidos Ftálicos/toxicidade , Receptores de Estrogênio/efeitos dos fármacos , Animais , Aromatase/efeitos dos fármacos , Células CHO/efeitos dos fármacos , Cricetulus , Relação Dose-Resposta a Droga , Ensaio de Desvio de Mobilidade Eletroforética , Feminino , Imunofluorescência , Humanos , Células MCF-7/efeitos dos fármacos , Ácidos Ftálicos/farmacologia , Reação em Cadeia da Polimerase , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Testosterona/farmacologia , Regulação para Cima/efeitos dos fármacos , Útero/efeitos dos fármacos , Vagina/efeitos dos fármacosRESUMO
Chemotherapy and anti-hormonal therapies are the most common treatments for non-organ-confined prostate cancer (PCa). However, the effectiveness of these therapies is limited, thus necessitating the development of alternative approaches. The present study focused on analyzing the role of pterostilbene (PTER)-isothiocyanate (ITC) conjugate--a novel class of hybrid compound synthesized by appending an ITC moiety on PTER backbone--in regulating the functions of androgen receptor (AR), thereby causing apoptosis of PCa cells. The conjugate molecule caused 50% growth inhibition (IC50) at 40 ± 1.12 and 45 ± 1.50 µM in AR positive (LNCaP) and negative (PC-3) cells, respectively. The reduced proliferation of PC-3 as well as LNCaP cells by conjugate correlated with accumulation of cells in G2/M phase and induction of caspase dependent apoptosis. Both PI3K/Akt and MAPK/ERK pathways played an important and differential role in conjugate-induced apoptosis of these PCa cells. While the inhibitor of Akt (A6730) or Akt-specific small interference RNA (siRNA) greatly sensitized PC-3 cells to conjugate-induced apoptosis, on the contrary, apoptosis was accelerated by inhibition of ERK (by PD98059 or ERK siRNA) in case of LNCaP cells, both ultimately culminating in the expression of cleaved caspase-3 protein. Moreover, anti-androgenic activity of the conjugate was mediated by decreased expression of AR and its co-activators (SRC-1, GRIP-1), thus interfering in their interactions with AR. All these data suggests that conjugate-induced inhibition of cell proliferation and induction of apoptosis are partly mediated by the down regulation of AR, Akt, and ERK signaling. These observations provide a rationale for devising novel therapeutic approaches for treating PCa by using conjugate alone or in combination with other therapeutics.
Assuntos
Proliferação de Células/efeitos dos fármacos , Isotiocianatos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Estilbenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Células CHO , Células COS , Caspase 3/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Chlorocebus aethiops , Cricetulus , Regulação para Baixo/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Naturally occurring pterostilbene (PTER) and isothiocyanate (ITC) attract great attention due to their wide range of biological properties, including anti-cancer, anti-leukemic, anti-bacterial and anti-inflammatory activities. A novel class of hybrid compound synthesized by introducing an ITC moiety on PTER backbone was evaluated for its anti-cancer efficacy in hormone-dependent breast cancer cell line (MCF-7) in vitro and Ehrlich ascitic tumor bearing mice model in vivo. The novel hybrid molecule showed significant in vitro anti-cancer activity (IC50=25 ± 0.38) when compared to reference compound PTER (IC50=65 ± 0.42). The conjugate molecule induced both S and G2/M phase cell cycle arrest as indicated by flow cytometry analysis. In addition, the conjugate induced cell death was characterized by changes in cell morphology, DNA fragmentation, activation of caspase-9, release of cytochrome-c into cytosol and increased Bax: Bcl-2 ratio. The conjugate also suppressed the phosphorylation of Akt and ERK. The conjugate induced cell death was significantly increased in presence of A6730 (a potent Akt1/2 kinase inhibitor) and PD98059 (a specific ERK inhibitor). Moreover, the conjugated PTER inhibited tumor growth in Ehrlich ascitic cell induced tumor bearing mice as observed by reduction in tumor volume compared to untreated animals. Collectively, the pro-apoptotic effect of conjugate is mediated through the activation of caspases, and is correlated with the blockade of the Akt and ERK signaling pathways in MCF-7 cells.
Assuntos
Carcinoma de Ehrlich/patologia , Proliferação de Células/efeitos dos fármacos , Isotiocianatos/farmacologia , Estilbenos/farmacologia , Animais , Regulação para Baixo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Células Hep G2 , Humanos , Isotiocianatos/química , Células MCF-7 , Masculino , Camundongos , Estilbenos/química , Carga Tumoral/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
Endocrine disrupting chemicals are the natural/synthetic compounds which mimic or inhibit the actions of endogenous hormones. Organotin compounds, such as tributyltin (TBT) are typical environmental contaminants and suspected endocrine-disrupting chemical. The present study evaluates the estrogenic potential of this compound in vitro in ER (+) breast adenocarcinoma, MCF-7 cell line. Our data showed that tributyltin chloride (TBTCl) had agonistic activities for estrogen receptor-α (ER-α). Its estrogenic potential was checked using cell proliferation assay, aromatase assay, transactivation assay, and protein expression analysis. Low dose treatment of TBTCl had a proliferative effect on MCF-7 cells and resulted in up-regulation of aromatase enzyme activity and enhanced estradiol production in MCF-7 cells. Immunofluorescence staining showed translocation of ER-α from cytoplasm to nucleus and increased expression of ER-α, 3ß-HSD and aromatase on treatment with increasing doses of TBTCl. Further, to decipher the probable signaling pathways involved in its action, the MCF-7 cells were transfected with different pathway dependent luciferase reporter plasmids (CRE, SRE, NF-κB and AP1). A significant increase in CRE and SRE and decrease in NF-κB regulated pathway were observed (p<0.05). Our results thus showed that the activation of SRE by TBTCl may be due to ligand dependent ER-α activation of the MAPK pathway and increased phosphorylation of ERK. In summary, the present data suggests that low dose of tributyltin genomically and non-genomically augmented estrogen dependent signaling by targeting various pathways.