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Sarah Natalie Cirilo Gimenes
Instituto Butantan

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Journal article
Published: 19 January 2021 in Semina: Ciências Agrárias
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Bacterial resistance is a sanitary issue explained by indiscriminate use of nonprescription drugs, and antimicrobial use in food production for growth promotion. Bothropstoxin-I (BthTx-I) is a phospholipase A2 (PLA2) from Bothrops jararacussu venom, which has a known antimicrobial effect. The goal of this study was the unprecedented evaluation of in vivo antimicrobial activity of BthTx-I in broilers. Microbiological, biochemical, and histological parameters were determined using 84 21-day old broilers that were kept in cages with four birds each at a density of 625 cm2/broiler. The experiment was randomized by three treatments with seven repetitions of four broilers each that lasted seven days. The treatments were: 1) bacitracin zinc diet; 2) PLA2-BthTx-I; 3) without additives. The data obtained from the studied variables was subjected to analysis of variance and an F-test at the 5% significance level. Averages of each variable in each treatment were compared by Tukey’s test. Broiler bacterial cloacal counts showed that BthTx-I decreased the microbial population without reducing body weight, intestinal morphology, or liver or kidney histopathological damage. The toxin showed in vivo activity, being an alternative for better performance in the production of broiler chickens, because it acted by decreasing the microbial load of potentially pathogenic bacteria in the intestinal microbiota of the birds and did not cause muscle, liver or kidney damage at the assessed dosage.

ACS Style

Ana Carolina Portella Silveira; Instituto Federal Do Triângulo Mineiro; Sarah Natalie Cirilo Gimenes; Luiz Fernando Barbaresco; Camila Perdoncini Carvalho; João Paulo Rodrigues Bueno; Ednaldo Carvalho Guimarães; Paulo Fernando Alves De Freitas; Mara Regina Bueno De Mattos Nascimento; Robson Carlos Antunes; Veridiana De Melo Rodrigues Ávila; Instituto Butantan; Faculdade Pitágoras; Universidade de São Paulo; Centro Universitário Do Triângulo; Universidade Federal de Uberlândia; Yes Nutrition. Antimicrobial effect of bothropstoxin-i in broilers. Semina: Ciências Agrárias 2021, 42, 267 -282.

AMA Style

Ana Carolina Portella Silveira, Instituto Federal Do Triângulo Mineiro, Sarah Natalie Cirilo Gimenes, Luiz Fernando Barbaresco, Camila Perdoncini Carvalho, João Paulo Rodrigues Bueno, Ednaldo Carvalho Guimarães, Paulo Fernando Alves De Freitas, Mara Regina Bueno De Mattos Nascimento, Robson Carlos Antunes, Veridiana De Melo Rodrigues Ávila, Instituto Butantan, Faculdade Pitágoras, Universidade de São Paulo, Centro Universitário Do Triângulo, Universidade Federal de Uberlândia, Yes Nutrition. Antimicrobial effect of bothropstoxin-i in broilers. Semina: Ciências Agrárias. 2021; 42 (1):267-282.

Chicago/Turabian Style

Ana Carolina Portella Silveira; Instituto Federal Do Triângulo Mineiro; Sarah Natalie Cirilo Gimenes; Luiz Fernando Barbaresco; Camila Perdoncini Carvalho; João Paulo Rodrigues Bueno; Ednaldo Carvalho Guimarães; Paulo Fernando Alves De Freitas; Mara Regina Bueno De Mattos Nascimento; Robson Carlos Antunes; Veridiana De Melo Rodrigues Ávila; Instituto Butantan; Faculdade Pitágoras; Universidade de São Paulo; Centro Universitário Do Triângulo; Universidade Federal de Uberlândia; Yes Nutrition. 2021. "Antimicrobial effect of bothropstoxin-i in broilers." Semina: Ciências Agrárias 42, no. 1: 267-282.

Journal article
Published: 28 July 2020 in International Journal of Biological Macromolecules
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Phospholipase A2 plays an important role in many diseases. Thus, the production of bioactive molecules, which can modulate PLA2 activity, became an important target for the pharmaceutical industry. Previously, we demonstrated the inhibitory and anti-angiogenic effect of γCdcPLI, the natural PLA2inhibitor from Crotalus durissus collilineatus. The aim of the present study was to recombinantly express the γCdcPLI inhibitor and analyze its biochemical and functional characteristics. Based on the amino acid sequence from the natural protein, we designed a synthetic gene for production of a non-tagged recombinant recγCdcPLI using the pHis-Parallel2 vector. To enable disulfide bond formation, protein expression was performed using E. coli Rosetta-gamiB. The protein was purified by anion and affinity chromatography with a yield of 5 mg/l. RecγCdcPLI showed similar secondary structure in CD and FTIR, revealing predominately β-strands. Analogous to the natural protein, recγCdcPLI was able to form oligomers of ~5.5 nm. The inhibitor was efficiently binding to PLA2 from honeybee (Kd = 1.48 μM) and was able to inhibit the PLA2 activity. Furthermore, it decreased the vessel formation in HUVEC cells, suggesting an anti-angiogenic potential. Heterologous production of recγCdcPLI is highly efficient and thus enables enhanced drug design for treatment of diseases triggered by PLA2 activity.

ACS Style

Sarah Natalie Cirilo Gimenes; Lorenz Aglas; Sabrina Wildner; Sara Huber; Ana Carolina Portella Silveira; Daiana Silva Lopes; Renata Santos Rodrigues; Luiz Ricardo Goulart; Peter Briza; Fatima Ferreira; Veridiana De Melo Rodrigues Ávila; Gabriele Gadermaier. Biochemical and functional characterization of a new recombinant phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum. International Journal of Biological Macromolecules 2020, 164, 1545 -1553.

AMA Style

Sarah Natalie Cirilo Gimenes, Lorenz Aglas, Sabrina Wildner, Sara Huber, Ana Carolina Portella Silveira, Daiana Silva Lopes, Renata Santos Rodrigues, Luiz Ricardo Goulart, Peter Briza, Fatima Ferreira, Veridiana De Melo Rodrigues Ávila, Gabriele Gadermaier. Biochemical and functional characterization of a new recombinant phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum. International Journal of Biological Macromolecules. 2020; 164 ():1545-1553.

Chicago/Turabian Style

Sarah Natalie Cirilo Gimenes; Lorenz Aglas; Sabrina Wildner; Sara Huber; Ana Carolina Portella Silveira; Daiana Silva Lopes; Renata Santos Rodrigues; Luiz Ricardo Goulart; Peter Briza; Fatima Ferreira; Veridiana De Melo Rodrigues Ávila; Gabriele Gadermaier. 2020. "Biochemical and functional characterization of a new recombinant phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum." International Journal of Biological Macromolecules 164, no. : 1545-1553.

Research article
Published: 08 June 2020 in PLOS Neglected Tropical Diseases
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Snake venoms are complex mixtures of proteins with toxic activities, with many distinct isoforms, affecting different physiological targets, comprised in a few protein families. It is currently accepted that this diversity in venom composition is an adaptive advantage for venom efficacy on a wide range of prey. However, on the other side, variability on isoforms expression has implications in the clinics of human victims of snakebites and in the efficacy of antivenoms. B. atrox snakes are responsible for most of the human accidents in Brazilian Amazon and the type and abundance of protein families on their venoms present individual variability. Thus, in this study we attempted to correlate the individual venom proteome of the snake brought to the hospital by the patient seeking for medical assistance with the clinical signs observed in the same patient. Individual variability was confirmed in venoms of the 14 snakes selected for the study. The abundance of each protein family was quite similar among the venom samples, while the isoforms composition was highly variable. Considering the protein families, the SVMP group presented the best correlation with bleeding disorders and edema. Considering individual isoforms, some isoforms of venom metalloproteinase (SVMP), C-type lectin-like toxins (CTL) and snake venom serine proteinases (SVSP) presented expression levels that with statistically significant positive correlation to signs and symptoms presented by the patients as bleeding disorders, edema, ecchymosis and blister formation. However, some unexpected data were also observed as the correlation between a CTL, CRISP or LAAO isoforms with blister formation, still to be confirmed with a larger number of samples. Although this is still a small number of patient samples, we were able to indicate that venom composition modulates clinical manifestations of snakebites, to confirm at the bedside the prominent role of SVMPs and to include new possible toxin candidates for the development of toxin inhibitors or to improve antivenom selectiveness, important actions for the next generation treatments of snakebites.

ACS Style

Ana Maria Moura-Da-Silva; Jorge Carlos Contreras-Bernal; Sarah Natalie Cirilo Gimenes; Luciana Aparecida Freitas-De-Sousa; José Antonio Portes-Junior; Pedro Da Silva Peixoto; Leo Kei Iwai; Valéria Mourão De Moura; Pedro Ferreira Bisneto; Marcus Lacerda; Iran Mendonça Da Silva; Luiz Carlos De Lima Ferreira; Sâmella Silva De Oliveira; Fan Hui Wen; Jacqueline De Almeida Gonçalves Sachett; Wuelton M. Monteiro. The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox). PLOS Neglected Tropical Diseases 2020, 14, e0008299 .

AMA Style

Ana Maria Moura-Da-Silva, Jorge Carlos Contreras-Bernal, Sarah Natalie Cirilo Gimenes, Luciana Aparecida Freitas-De-Sousa, José Antonio Portes-Junior, Pedro Da Silva Peixoto, Leo Kei Iwai, Valéria Mourão De Moura, Pedro Ferreira Bisneto, Marcus Lacerda, Iran Mendonça Da Silva, Luiz Carlos De Lima Ferreira, Sâmella Silva De Oliveira, Fan Hui Wen, Jacqueline De Almeida Gonçalves Sachett, Wuelton M. Monteiro. The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox). PLOS Neglected Tropical Diseases. 2020; 14 (6):e0008299.

Chicago/Turabian Style

Ana Maria Moura-Da-Silva; Jorge Carlos Contreras-Bernal; Sarah Natalie Cirilo Gimenes; Luciana Aparecida Freitas-De-Sousa; José Antonio Portes-Junior; Pedro Da Silva Peixoto; Leo Kei Iwai; Valéria Mourão De Moura; Pedro Ferreira Bisneto; Marcus Lacerda; Iran Mendonça Da Silva; Luiz Carlos De Lima Ferreira; Sâmella Silva De Oliveira; Fan Hui Wen; Jacqueline De Almeida Gonçalves Sachett; Wuelton M. Monteiro. 2020. "The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox)." PLOS Neglected Tropical Diseases 14, no. 6: e0008299.

Journal article
Published: 02 February 2020 in Toxins
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Snake venom metalloproteinases (SVMPs) play an important role in local tissue damage of snakebite patients, mostly by hydrolysis of basement membrane (BM) components. We evaluated the proinflammatory activity of SVMPs Atroxlysin-Ia (ATXL) and Batroxrhagin (BATXH) from Bothrops atrox venom and their hydrolysis products of Matrigel. BALB/c mice were injected with SVMPs (2 μg), for assessment of paw edema and peritoneal leukocyte accumulation. Both SVMPs induced edema, representing an increase of ~70% of the paw size. Leukocyte infiltrates reached levels of 6 × 106 with ATXL and 5 × 106 with BATXH. TNF-α was identified in the supernatant of BATXH—or venom-stimulated MPAC cells. Incubation of Matrigel with the SVMPs generated fragments, including peptides from Laminin, identified by LC–MS/MS. The Matrigel hydrolysis peptides caused edema that increased 30% the paw size and promoted leukocyte accumulation (4–5 × 106) to the peritoneal cavity, significantly higher than Matrigel control peptides 1 and 4 h after injection. Our findings suggest that ATXL and BATXH are involved in the inflammatory reaction observed in B. atrox envenomings by direct action on inflammatory cells or by releasing proinflammatory peptides from BM proteins that may amplify the direct action of SVMPs through activation of endogenous signaling pathways.

ACS Style

Michelle Teixeira De Almeida; Luciana Aparecida Freitas-De-Sousa; Monica Colombini; Sarah Gimenes; Eduardo S. Kitano; Eliana L. Faquim-Mauro; Solange M. T. Serrano; Ana Maria Moura-Da-Silva. Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components. Toxins 2020, 12, 96 .

AMA Style

Michelle Teixeira De Almeida, Luciana Aparecida Freitas-De-Sousa, Monica Colombini, Sarah Gimenes, Eduardo S. Kitano, Eliana L. Faquim-Mauro, Solange M. T. Serrano, Ana Maria Moura-Da-Silva. Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components. Toxins. 2020; 12 (2):96.

Chicago/Turabian Style

Michelle Teixeira De Almeida; Luciana Aparecida Freitas-De-Sousa; Monica Colombini; Sarah Gimenes; Eduardo S. Kitano; Eliana L. Faquim-Mauro; Solange M. T. Serrano; Ana Maria Moura-Da-Silva. 2020. "Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components." Toxins 12, no. 2: 96.

Journal article
Published: 24 October 2019 in Current Topics in Medicinal Chemistry
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Background: Disintegrins from snake venoms bind with high specificity cell surface integrins, which are important pharmacological targets associated with cancer development and progression. Objective: In this study, we isolated a disintegrin from the Porthidium lansbergii lansbergii venom and evaluated its antitumoral effects on breast cancer cells. Methods: The isolation of the disintegrin was performed on RP-HPLC and the inhibition of platelet aggregation was evaluated on human platelet-rich plasma. The inhibition of cell adhesion was also evaluated in vitro on cultures of cell lines by the MTT method as well as the inhibition of breast cancer cell migration by the wound healing assay. The binding of the disintegrin to integrin subunits was verified by flow cytometry and confocal microscopy. Finally, inhibition of angiogenesis was assessed in vitro on HUVEC cells and the concentration of VEGF was measured in the cellular supernatants. Results: The disintegrin, named Lansbermin-I, is a low molecular weight protein (< 10 kDa) that includes an RGD on its sequence identified previously. Lansbermin-I showed potent inhibition of ADP and collagen-induced platelet aggregation on human plasma and also displayed inhibitory effects on the adhesion and migration of breast cancer MCF7 and MDA-MB 231cell lines, without affecting nontumorigenic breast MCF-10A and lung BEAS cells. Additionally, Lansbermin-I prevented MCF7 cells to adhere to fibronectin and collagen, and also inhibited in vitro angiogenesis on human endothelial HUVEC cells. Conclusion: Our results display the first report on the antitumor and anti-metastatic effects of an RGDdisintegrin isolated from a Porthidium snake venom by possibly interfering with α2 and/or β1-containing integrins. Thus, Lansbermin-I could be an attractive model to elucidate the role of disintegrins against breast cancer development.

ACS Style

Leonel Montealegre-Sánchez; Sarah Gimenes; Daiana S. Lopes; Samuel Cota Teixeira; Luis Solano-Redondo; Veridiana De Melo Rodrigues; Eliécer Jiménez Charris. Antitumoral Potential of Lansbermin-I, a Novel Disintegrin from Porthidium lansbergii lansbergii Venom on Breast Cancer Cells. Current Topics in Medicinal Chemistry 2019, 19, 2069 -2078.

AMA Style

Leonel Montealegre-Sánchez, Sarah Gimenes, Daiana S. Lopes, Samuel Cota Teixeira, Luis Solano-Redondo, Veridiana De Melo Rodrigues, Eliécer Jiménez Charris. Antitumoral Potential of Lansbermin-I, a Novel Disintegrin from Porthidium lansbergii lansbergii Venom on Breast Cancer Cells. Current Topics in Medicinal Chemistry. 2019; 19 (22):2069-2078.

Chicago/Turabian Style

Leonel Montealegre-Sánchez; Sarah Gimenes; Daiana S. Lopes; Samuel Cota Teixeira; Luis Solano-Redondo; Veridiana De Melo Rodrigues; Eliécer Jiménez Charris. 2019. "Antitumoral Potential of Lansbermin-I, a Novel Disintegrin from Porthidium lansbergii lansbergii Venom on Breast Cancer Cells." Current Topics in Medicinal Chemistry 19, no. 22: 2069-2078.

Journal article
Published: 22 May 2019 in International Journal of Biological Macromolecules
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This work shows the antitumor and antimetastatic effects of BthTX-II, an Asp-49 PLA2 from Bothrops jararacussu venom, on MDA-MB-231 human triple negative breast cancer cells. BthTX-II caused a dose-dependent cell death of MDA-MB-231 cells when compared with the non-tumorigenic breast cells by inducing apoptosis and autophagy. BthTX-II was also able to decrease the proliferation and to inhibit cell cycle progression. We also observed an upregulation of the ATM gene, which is responsible for cell-cycle arrest and DNA repair such as CCND1, CCNE1, CDC25A, E2F1, AKT1 and AKT3. Interestingly, BthTX-II inhibited invasion, migration and 3D cell growth of MDA-MB-231 cells, as well as inhibited the epithelial–mesenchymal transition (EMT) of this cell by increasing E-cadherin (CDH-1) and decreasing TWIST1, CTNNB1, vimentin and cytokeratin-5 expression. In conclusion, these results showed that BthTX-II displays antitumor and antimetastatic effects on MDA-MB-231 cells and may be useful for the development of new approaches and therapeutic strategies to manage triple negative breast cancer.

ACS Style

Fernanda Van Petten De Vasconcelos Azevedo; Mariana Alves Pereira Zóia; Daiana Silva Lopes; Sarah Gimenes; Lara Vecchi; Patrícia Terra Alves; Renata Santos Rodrigues; Anielle Christine A. Silva; Kelly Aparecida G. Yoneyama; Luiz Ricardo Goulart; Veridiana De Melo Rodrigues. Antitumor and antimetastatic effects of PLA2-BthTX-II from Bothrops jararacussu venom on human breast cancer cells. International Journal of Biological Macromolecules 2019, 135, 261 -273.

AMA Style

Fernanda Van Petten De Vasconcelos Azevedo, Mariana Alves Pereira Zóia, Daiana Silva Lopes, Sarah Gimenes, Lara Vecchi, Patrícia Terra Alves, Renata Santos Rodrigues, Anielle Christine A. Silva, Kelly Aparecida G. Yoneyama, Luiz Ricardo Goulart, Veridiana De Melo Rodrigues. Antitumor and antimetastatic effects of PLA2-BthTX-II from Bothrops jararacussu venom on human breast cancer cells. International Journal of Biological Macromolecules. 2019; 135 ():261-273.

Chicago/Turabian Style

Fernanda Van Petten De Vasconcelos Azevedo; Mariana Alves Pereira Zóia; Daiana Silva Lopes; Sarah Gimenes; Lara Vecchi; Patrícia Terra Alves; Renata Santos Rodrigues; Anielle Christine A. Silva; Kelly Aparecida G. Yoneyama; Luiz Ricardo Goulart; Veridiana De Melo Rodrigues. 2019. "Antitumor and antimetastatic effects of PLA2-BthTX-II from Bothrops jararacussu venom on human breast cancer cells." International Journal of Biological Macromolecules 135, no. : 261-273.

Full paper
Published: 26 April 2019 in ChemBioChem
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Class 1 myosins (Myo1s) were the first unconventional myosins identified and humans have eight known Myo1 isoforms. The Myo1 family is involved in the regulation of gene expression, cytoskeletal rearrangements, delivery of proteins to the cell surface, cell migration and spreading. Thus, the important role of Myo1s in different biological processes is evident. In this study, we have investigated the effects of pentachloropseudilin (PClP), a reversible and allosteric potent inhibitor of Myo1s, on angiogenesis. We demonstrated that treatment of cells with PClP promoted a decrease in the number of vessels. The observed inhibition of angiogenesis is likely to be related to the inhibition of cell proliferation, migration and adhesion, as well as to alteration of the actin cytoskeleton pattern, as shown on a PClP‐treated HUVEC cell line. Moreover, we also demonstrated that PClP treatment partially prevented the delivery of integrins to the plasma membrane. Finally, we showed that PClP caused DNA strand breaks, which are probably repaired during the cell cycle arrest in the G1 phase. Taken together, our results suggest that Myo1s participate directly in the angiogenesis process.

ACS Style

Samuel Cota Teixeira; Daiana Silva Lopes; Marcelo S. da Silva; Felipe Andrés Cordero Da Luz; Sarah Gimenes; Bruna Cristina Borges; Aline Alves Da Silva; Flávia Alves Martins; Marlus Alves Dos Santos; Thaise Teixeira; Ricardo A. Oliveira; Veridiana De Melo Rodrigues Ávila; Maria Carolina Elias; René Martin; Dr. Claudio Vieira Da Silva; Dr. Hans‐Joachim Knölker. Pentachloropseudilin Impairs Angiogenesis by Disrupting the Actin Cytoskeleton, Integrin Trafficking and the Cell Cycle. ChemBioChem 2019, 20, 2390 -2401.

AMA Style

Samuel Cota Teixeira, Daiana Silva Lopes, Marcelo S. da Silva, Felipe Andrés Cordero Da Luz, Sarah Gimenes, Bruna Cristina Borges, Aline Alves Da Silva, Flávia Alves Martins, Marlus Alves Dos Santos, Thaise Teixeira, Ricardo A. Oliveira, Veridiana De Melo Rodrigues Ávila, Maria Carolina Elias, René Martin, Dr. Claudio Vieira Da Silva, Dr. Hans‐Joachim Knölker. Pentachloropseudilin Impairs Angiogenesis by Disrupting the Actin Cytoskeleton, Integrin Trafficking and the Cell Cycle. ChemBioChem. 2019; 20 (18):2390-2401.

Chicago/Turabian Style

Samuel Cota Teixeira; Daiana Silva Lopes; Marcelo S. da Silva; Felipe Andrés Cordero Da Luz; Sarah Gimenes; Bruna Cristina Borges; Aline Alves Da Silva; Flávia Alves Martins; Marlus Alves Dos Santos; Thaise Teixeira; Ricardo A. Oliveira; Veridiana De Melo Rodrigues Ávila; Maria Carolina Elias; René Martin; Dr. Claudio Vieira Da Silva; Dr. Hans‐Joachim Knölker. 2019. "Pentachloropseudilin Impairs Angiogenesis by Disrupting the Actin Cytoskeleton, Integrin Trafficking and the Cell Cycle." ChemBioChem 20, no. 18: 2390-2401.

Journal article
Published: 01 October 2018 in International Journal of Biological Macromolecules
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Herein we evaluated the genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) from Bothrops pauloensis, on breast cancer cells. BnSP-6 was able to induce a higher cytotoxic and genotoxic activity in MDA-MB-231 cells, when compared to MCF10A (a non-tumorigenic breast cell line), suggesting that this protein presented a possible preference for cancer cells. BnSP-6 inhibited MDA-MB-231 proliferation at 24, 48 and 72 h. In addition, BnSP-6 induced significant increase in the percentage of TUNEL-positive cells, a marker of DNA damage. To obtain novel insight into the direct DNA damage interference in MDA-MB-231 survival and proliferation, we evaluated cell cycle progression. BnSP-6 produced a significant decrease in 2N (G1) and an increase in the G2/M phase and this capacity is likely related to the modulation of expression of progression cell cycle-associated genes (CCND1, CCNE1, CDC25A, CHEK2, E2F1, CDH-1 and NF-kB). Taken together, these results indicate that BnSP-6 induces DNA damage in breast cancer cells and is an attractive model for developing innovative therapeutic agents against breast cancer.

ACS Style

Makswell Almeida Silva; Daiana Lopes; Samuel Cota Teixeira; Sarah Gimenes; Fernanda Van Petten De Vasconcelos Azevedo; Lorena Polloni; Bruna Cristina Borges; Marcelo S. da Silva; Marcelo José Barbosa; Robson José De Oliveira Júnior; Maria Carolina Elias; Claudio Vieira da Silva; Kelly Aparecida Geraldo Yoneyama; Veridiana De Melo Rodrigues; Renata Santos Rodrigues. Genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) homologue from Bothrops pauloensis snake venom, on MDA-MB-231 breast cancer cells. International Journal of Biological Macromolecules 2018, 118, 311 -319.

AMA Style

Makswell Almeida Silva, Daiana Lopes, Samuel Cota Teixeira, Sarah Gimenes, Fernanda Van Petten De Vasconcelos Azevedo, Lorena Polloni, Bruna Cristina Borges, Marcelo S. da Silva, Marcelo José Barbosa, Robson José De Oliveira Júnior, Maria Carolina Elias, Claudio Vieira da Silva, Kelly Aparecida Geraldo Yoneyama, Veridiana De Melo Rodrigues, Renata Santos Rodrigues. Genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) homologue from Bothrops pauloensis snake venom, on MDA-MB-231 breast cancer cells. International Journal of Biological Macromolecules. 2018; 118 ():311-319.

Chicago/Turabian Style

Makswell Almeida Silva; Daiana Lopes; Samuel Cota Teixeira; Sarah Gimenes; Fernanda Van Petten De Vasconcelos Azevedo; Lorena Polloni; Bruna Cristina Borges; Marcelo S. da Silva; Marcelo José Barbosa; Robson José De Oliveira Júnior; Maria Carolina Elias; Claudio Vieira da Silva; Kelly Aparecida Geraldo Yoneyama; Veridiana De Melo Rodrigues; Renata Santos Rodrigues. 2018. "Genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) homologue from Bothrops pauloensis snake venom, on MDA-MB-231 breast cancer cells." International Journal of Biological Macromolecules 118, no. : 311-319.

Journal article
Published: 12 September 2018 in International Journal of Biological Macromolecules
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This work shows for the first time the antitumoral and angiostatic potential effects of Pllans–II, an acidic monomeric Asp49–PLA2 from Porthidium lansbergii lansbergii snake venom on HeLa cells. Pllans–II exhibited a predominant dose–dependent cytotoxicity on cervical carcinoma HeLa cells more than human breast cancer MCF7 and MDA–MB–231 cells. Interestingly, Pllans–II showed negligible effect in vitro on normal cells such as MCF 10A, a non–tumorigenic breast epithelial cell and endothelial cells–HUVEC. Besides, Pllans–II induced a significative cell cycle arrest in G1 phase of treated HeLa. Flow Cytometry analysis showed that Pllans–II induced both early and late apoptosis on HeLa cells, verified by the modulation of important genes mediators of apoptosis pathways such as CASP8, BCL2L1, BCL2, BAX, BAD and BIRC5, showing a possible apoptotic cell death triggered through extrinsic pathways. Pllans–II was also able to inhibit cell migration on HeLa cells by interfering with α5 and β1–containing integrins. In addition, Pllans–II inhibited in vitro angiogenesis on endothelial HUVEC cells through VEGF–independent pathway. Our results display that Pllans–II is able to be an anticancer target for the development of a new antitumoral prototype.

ACS Style

Eliécer Jiménez–Charris; Daiana Lopes; Sarah Gimenes; Samuel Cota Teixeira; Leonel Montealegre–Sánchez; Luis Solano–Redondo; Leonardo Fierro–Pérez; Veridiana De Melo Rodrigues Ávila. Antitumor potential of Pllans–II, an acidic Asp49–PLA2 from Porthidium lansbergii lansbergii snake venom on human cervical carcinoma HeLa cells. International Journal of Biological Macromolecules 2018, 122, 1053 -1061.

AMA Style

Eliécer Jiménez–Charris, Daiana Lopes, Sarah Gimenes, Samuel Cota Teixeira, Leonel Montealegre–Sánchez, Luis Solano–Redondo, Leonardo Fierro–Pérez, Veridiana De Melo Rodrigues Ávila. Antitumor potential of Pllans–II, an acidic Asp49–PLA2 from Porthidium lansbergii lansbergii snake venom on human cervical carcinoma HeLa cells. International Journal of Biological Macromolecules. 2018; 122 ():1053-1061.

Chicago/Turabian Style

Eliécer Jiménez–Charris; Daiana Lopes; Sarah Gimenes; Samuel Cota Teixeira; Leonel Montealegre–Sánchez; Luis Solano–Redondo; Leonardo Fierro–Pérez; Veridiana De Melo Rodrigues Ávila. 2018. "Antitumor potential of Pllans–II, an acidic Asp49–PLA2 from Porthidium lansbergii lansbergii snake venom on human cervical carcinoma HeLa cells." International Journal of Biological Macromolecules 122, no. : 1053-1061.

Journal article
Published: 01 November 2017 in Biologicals
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Polyclonal antibodies raised in Balb-c mice against BnSP-7, a Lys-49 phospholipase A2, were used to measure cross reactivity against other snake venoms. Using ELISA, these antibodies were able to recognize PLA2s isoforms present in venoms of botropic snakes at 1:6400, 1:3200 and 1:100 ratios (w/w). These antibodies highly recognized proteins of low molecular weight (∼14,000) from crude snake venom Bp and Bm by Western Blotting. PLA2 these venoms, by alignment of primary structures demonstrated high identity with BnSP-7 PLA2, especially in the C-terminal region. However, the crude snake venom Bd and Bj, showed low recognition. The PLA2 activity of Bothrops pauloensis, Bothrops moojeni venoms or BpPLA2-TXI was inhibited significantly when anti-BnSP-7 antibodies were incubated at 1:10 and 1:20 ratios (venoms or toxin:anti-BnSP-7, w/w), respectively. The myotoxic effect induced by the same venoms was also reduced significantly at 1:1, 1:10 and 1:20 ratios, by decreased creatine kinase levels. The anti-PLA2 polyclonal antibodies effectively recognized PLA2s from Bothrops pauloensis and Bothrops moojeni venoms, and neutralized specific catalytic and myotoxic activity.

ACS Style

Lamartine Lemos de Melo; Mirian Machado Mendes; Lívia M. Alves; Thais F. Isabel; Sâmela A.P.B. Vieira; Sarah Gimenes; Andreimar Soares; Veridiana De Melo Rodrigues; Luiz F.M. Izidoro. Cross-reactivity and inhibition myotoxic effects induced by Bothrops snake venoms using specific polyclonal anti -BnSP7 antibodies. Biologicals 2017, 50, 109 -116.

AMA Style

Lamartine Lemos de Melo, Mirian Machado Mendes, Lívia M. Alves, Thais F. Isabel, Sâmela A.P.B. Vieira, Sarah Gimenes, Andreimar Soares, Veridiana De Melo Rodrigues, Luiz F.M. Izidoro. Cross-reactivity and inhibition myotoxic effects induced by Bothrops snake venoms using specific polyclonal anti -BnSP7 antibodies. Biologicals. 2017; 50 ():109-116.

Chicago/Turabian Style

Lamartine Lemos de Melo; Mirian Machado Mendes; Lívia M. Alves; Thais F. Isabel; Sâmela A.P.B. Vieira; Sarah Gimenes; Andreimar Soares; Veridiana De Melo Rodrigues; Luiz F.M. Izidoro. 2017. "Cross-reactivity and inhibition myotoxic effects induced by Bothrops snake venoms using specific polyclonal anti -BnSP7 antibodies." Biologicals 50, no. : 109-116.

Journal article
Published: 01 September 2017 in International Journal of Biological Macromolecules
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The present work reports the effects of a C-type lectin (BpLec) isolated from Bothrops pauloensis snake venom upon in vitro and in vivo angiogenesis models. Initially, we noted that BpLec was not cytotoxic to endothelial cells (tEnd) in doses up to 40μg/mL, but lower doses (2.5μg/mL, 5μg/mL, 10μg/mL and 20μg/mL) reduced tEnd cells adhesion to some extracellular matrix proteins and inhibited the in vitro vessel formation in Matrigel assay stimulated by bFGF. β-galactosides (d-lactose, N-acetyl-d-galactosamine and d-galactose) at 400mM reversed the effect of BpLec on tEnd cells adhesion, whereas d-galactose (400mM) partially reversed BpLec property of inhibiting vessel formation by tEnd cells in Matrigel. In vivo assays showed that BpLec increased hemoglobin content and capillary vessels number in polyether-polyurethane sponge discs subcutaneously implanted into dorsal skin mice. Additionally, BpLec also reduced collagen deposition and did not induce a pro-inflammatory response, as demonstrated by the decreased the secretion of some inflammatory cytokines, whereas myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activities were not altered by BpLec. Taken together, our results indicate that BpLec might represent an interesting angiogenesis and inflammatory modulator that could also be used for searching possible therapeutic targets involved in these processes.

ACS Style

Letícia Eulalio Castanheira; Daiana Silva Lopes; Sarah Natalie Cirilo Gimenes; Simone Ramos Deconte; Bruno Antônio Ferreira; Patricia Terra Alves; Luiz Ricardo Goulart Filho; Tatiana Carla Tomiosso; Renata Santos Rodrigues; Kelly Aparecida Geraldo Yoneyama; Fernanda De Assis Araújo; Veridiana De Melo Rodrigues. Angiogenenic effects of BpLec, a C-type lectin isolated from Bothrops pauloensis snake venom. International Journal of Biological Macromolecules 2017, 102, 153 -161.

AMA Style

Letícia Eulalio Castanheira, Daiana Silva Lopes, Sarah Natalie Cirilo Gimenes, Simone Ramos Deconte, Bruno Antônio Ferreira, Patricia Terra Alves, Luiz Ricardo Goulart Filho, Tatiana Carla Tomiosso, Renata Santos Rodrigues, Kelly Aparecida Geraldo Yoneyama, Fernanda De Assis Araújo, Veridiana De Melo Rodrigues. Angiogenenic effects of BpLec, a C-type lectin isolated from Bothrops pauloensis snake venom. International Journal of Biological Macromolecules. 2017; 102 ():153-161.

Chicago/Turabian Style

Letícia Eulalio Castanheira; Daiana Silva Lopes; Sarah Natalie Cirilo Gimenes; Simone Ramos Deconte; Bruno Antônio Ferreira; Patricia Terra Alves; Luiz Ricardo Goulart Filho; Tatiana Carla Tomiosso; Renata Santos Rodrigues; Kelly Aparecida Geraldo Yoneyama; Fernanda De Assis Araújo; Veridiana De Melo Rodrigues. 2017. "Angiogenenic effects of BpLec, a C-type lectin isolated from Bothrops pauloensis snake venom." International Journal of Biological Macromolecules 102, no. : 153-161.

Journal article
Published: 01 August 2017 in Scientific Reports
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Phospholipases A2(PLA2s) overexpression is closely associated with the malignant potential of breast cancers. Here, we showed for the first the antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 cell. Firstly, γCdcPLI was more cytotoxic to MDA-MB-231 breast cancer cells than other cell lines (MCF-7, HeLa, PC3 and A549) and did not affect the viability of non-tumorigenic breast cell (MCF 10A). In addition, γCdcPLI induced modulation of important mediators of apoptosis pathways such as p53, MAPK-ERK, BIRC5 and MDM2. γCdcPLI decreased MDA-MB-231 adhesion, migration and invasion. Interestingly, the γCdcPLI also inhibited the adhesion and migration of endothelial cells and blocked angiogenesis by inhibiting tube formation by HUVECs in vitro and sprouting elongation on aortic ring assay ex vivo. Furthermore, γCdcPLI reduced the production of vascular endothelial growth factor (VEGF). γCdcPLI was also able to decrease PGE2 levels in MDA-MB-231 and inhibited gene and protein expression of the PI3K/Akt pathway. In conclusion, γCdcPLI showed in vitro antitumoral, antimestatatic and anti-angiogenic potential effects and could be an attractive approach for futures studies in cancer therapy.

ACS Style

Sarah N. C. Gimenes; Daiana S. Lopes; Patrícia Terra Alves; Fernanda Van Petten De Vasconcelos Azevedo; Lara Vecchi; Luiz R. Goulart; Thais C. S. Rodrigues; André L. Q. Santos; Vera L. De C. Brites; Thaise Teixeira; Cláudio V. Da Silva; Matheus H. Dias; Samuel Cota Teixeira; Renata S. Rodrigues; Kelly A. G. Yoneyama; Ricardo A. Oliveira; Veridiana De M. Rodrigues. Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell. Scientific Reports 2017, 7, 1 -15.

AMA Style

Sarah N. C. Gimenes, Daiana S. Lopes, Patrícia Terra Alves, Fernanda Van Petten De Vasconcelos Azevedo, Lara Vecchi, Luiz R. Goulart, Thais C. S. Rodrigues, André L. Q. Santos, Vera L. De C. Brites, Thaise Teixeira, Cláudio V. Da Silva, Matheus H. Dias, Samuel Cota Teixeira, Renata S. Rodrigues, Kelly A. G. Yoneyama, Ricardo A. Oliveira, Veridiana De M. Rodrigues. Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell. Scientific Reports. 2017; 7 (1):1-15.

Chicago/Turabian Style

Sarah N. C. Gimenes; Daiana S. Lopes; Patrícia Terra Alves; Fernanda Van Petten De Vasconcelos Azevedo; Lara Vecchi; Luiz R. Goulart; Thais C. S. Rodrigues; André L. Q. Santos; Vera L. De C. Brites; Thaise Teixeira; Cláudio V. Da Silva; Matheus H. Dias; Samuel Cota Teixeira; Renata S. Rodrigues; Kelly A. G. Yoneyama; Ricardo A. Oliveira; Veridiana De M. Rodrigues. 2017. "Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell." Scientific Reports 7, no. 1: 1-15.

Journal article
Published: 01 April 2017 in International Journal of Biological Macromolecules
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Breast cancer is a highly malignant carcinoma and remains the second leading cause of mortality among women. The antitumor effects of metalloproteinases and disintegrins from snake venom on various types of cancer cells have been investigated. In this study, we evaluated the antitumor and antiangiogenic effects on MDA-MB-231 human breast cancer cells and endothelial cells induced by Bothropoidin, a disintegrin-like metalloproteinase isolated from Bothrops pauloensis snake venom. At 24h after treatment at 100μg/mL, Bothropoidin exerted a moderate cytotoxic effect of 30% on MDA-MB-231 versus 10% cytotoxicity against MCF10A (a non-tumorigenic breast cell line), a significant difference that suggests a possible preference by this protein for targets in cancer cells. Early and late apoptosis of MDA-MB-231 was observed after Bothropoidin treatment (10μg/mL and 40μg/mL). Furthermore, this toxin inhibited not only the adhesion of MDA-MB-231 cells in a dose-dependent manner but also cell migration by approximately 45%. In addition, Bothropoidin decreased endothelial cells viability and adhesion in Matrigel and inhibited in vitro angiogenesis in Matrigel stimulated by bFGF, showing significantly fewer formed vessels. The results demonstrated that Bothropoidin has potent in vitro antitumor and antiangiogenic effect and represents a biotechnological tool for elucidating the antitumor effect of disintegrins-like metalloproteinases in cancer cells.

ACS Style

Denise De Oliveira Guimarães; Daiana Silva Lopes; Fernanda Van Petten De Vasconcelos Azevedo; Sarah Gimenes; Makswell Almeida Silva; David Collares Achê; Mário Sérgio Rocha Gomes; Lara Vecchi; Luiz Ricardo Goulart; Kelly Aparecida Geraldo Yoneyama; Renata Santos Rodrigues; Veridiana De Melo Rodrigues. In vitro antitumor and antiangiogenic effects of Bothropoidin, a metalloproteinase from Bothrops pauloensis snake venom. International Journal of Biological Macromolecules 2017, 97, 770 -777.

AMA Style

Denise De Oliveira Guimarães, Daiana Silva Lopes, Fernanda Van Petten De Vasconcelos Azevedo, Sarah Gimenes, Makswell Almeida Silva, David Collares Achê, Mário Sérgio Rocha Gomes, Lara Vecchi, Luiz Ricardo Goulart, Kelly Aparecida Geraldo Yoneyama, Renata Santos Rodrigues, Veridiana De Melo Rodrigues. In vitro antitumor and antiangiogenic effects of Bothropoidin, a metalloproteinase from Bothrops pauloensis snake venom. International Journal of Biological Macromolecules. 2017; 97 ():770-777.

Chicago/Turabian Style

Denise De Oliveira Guimarães; Daiana Silva Lopes; Fernanda Van Petten De Vasconcelos Azevedo; Sarah Gimenes; Makswell Almeida Silva; David Collares Achê; Mário Sérgio Rocha Gomes; Lara Vecchi; Luiz Ricardo Goulart; Kelly Aparecida Geraldo Yoneyama; Renata Santos Rodrigues; Veridiana De Melo Rodrigues. 2017. "In vitro antitumor and antiangiogenic effects of Bothropoidin, a metalloproteinase from Bothrops pauloensis snake venom." International Journal of Biological Macromolecules 97, no. : 770-777.

Journal article
Published: 21 March 2017 in Scientific Reports
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Chronic chagasic cardiomyopathy (CCC) is arguably the most important form of the Chagas Disease, caused by the intracellular protozoan Trypanosoma cruzi; it is estimated that 10–30% of chronic patients develop this clinical manifestation. The most common and severe form of CCC can be related to ventricular abnormalities, such as heart failure, arrhythmias, heart blocks, thromboembolic events and sudden death. Therefore, in this study, we proposed to evaluate the anti-angiogenic activity of a recombinant protein from T. cruzi named P21 (rP21) and the potential impact of the native protein on CCC. Our data suggest that the anti-angiogenic activity of rP21 depends on the protein’s direct interaction with the CXCR4 receptor. This capacity is likely related to the modulation of the expression of actin and angiogenesis-associated genes. Thus, our results indicate that T. cruzi P21 is an attractive target for the development of innovative therapeutic agents against CCC.

ACS Style

Samuel Cota Teixeira; Daiana Silva Lopes; Sarah Natalie Cirilo Gimenes; Thaise Teixeira; Marcelo Santos Da Silva; Rebecca Tavares E Silva Brígido; Felipe Andrés Cordero Da Luz; Aline Alves Da Silva; Makswell Almeida Silva; Pilar Veras Florentino; Paula Cristina Brígido Tavares; Marlus Alves Dos Santos; Veridiana De Melo Rodrigues; Marcelo José Barbosa Silva; Maria Carolina Elias; Renato Arruda Mortara; Claudio Vieira Da Silva. Mechanistic Insights into the Anti-angiogenic Activity of Trypanosoma cruzi Protein 21 and its Potential Impact on the Onset of Chagasic Cardiomyopathy. Scientific Reports 2017, 7, 44978 .

AMA Style

Samuel Cota Teixeira, Daiana Silva Lopes, Sarah Natalie Cirilo Gimenes, Thaise Teixeira, Marcelo Santos Da Silva, Rebecca Tavares E Silva Brígido, Felipe Andrés Cordero Da Luz, Aline Alves Da Silva, Makswell Almeida Silva, Pilar Veras Florentino, Paula Cristina Brígido Tavares, Marlus Alves Dos Santos, Veridiana De Melo Rodrigues, Marcelo José Barbosa Silva, Maria Carolina Elias, Renato Arruda Mortara, Claudio Vieira Da Silva. Mechanistic Insights into the Anti-angiogenic Activity of Trypanosoma cruzi Protein 21 and its Potential Impact on the Onset of Chagasic Cardiomyopathy. Scientific Reports. 2017; 7 (1):44978.

Chicago/Turabian Style

Samuel Cota Teixeira; Daiana Silva Lopes; Sarah Natalie Cirilo Gimenes; Thaise Teixeira; Marcelo Santos Da Silva; Rebecca Tavares E Silva Brígido; Felipe Andrés Cordero Da Luz; Aline Alves Da Silva; Makswell Almeida Silva; Pilar Veras Florentino; Paula Cristina Brígido Tavares; Marlus Alves Dos Santos; Veridiana De Melo Rodrigues; Marcelo José Barbosa Silva; Maria Carolina Elias; Renato Arruda Mortara; Claudio Vieira Da Silva. 2017. "Mechanistic Insights into the Anti-angiogenic Activity of Trypanosoma cruzi Protein 21 and its Potential Impact on the Onset of Chagasic Cardiomyopathy." Scientific Reports 7, no. 1: 44978.

Journal article
Published: 01 January 2016 in International Journal of Biological Macromolecules
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This work shows the antitumoral effects of BnSP-6, a Lys 49 PLA2 isolated from Bothrops pauloensis venom, on human breast cancer MDA-MB-231 cells. BnSP-6 caused a dose-dependent cytotoxicity and inhibited cell adhesion. Interestingly, cytotoxic activity of BnSP-6 was significantly lower against MCF10A, a non-tumorigenic breast cell line, suggesting that this PLA2 presented a possible preference for targets in cancer cells. Analysis of cell death on MDA-MB-231 cells showed that BnSP-6 stimulated the autophagy process, as evidenced by labeling of autophagic vacuoles. Moreover, apoptosis assays showed that BnSP-6 induced both early and late apoptosis. Apoptosis of MDA-MB-231 cells was also confirmed by up-regulation of different genes related to the apoptosis pathway, such as TNF, TNFRSF10B, TNFRSF1A and CASP8 and decreased expression of anti-apoptotic genes (BCL2 and BCL2L). In addition, BnSP-6 caused a remarkable increase in gene expression of BRCA2 and TP53 tumor suppressors. Finally, BnSP-6 induced down-regulation of Angiopoetin 1 gene (potent pro-angiogenic factor) and inhibited adhesion and migration of MDA-MB-231 cells suggesting pharmaceutical applications of this PLA2 as an antiangiogenic and anti-metastatic agent. Taken together, our results show that the PLA2 BnSP-6 presents anticancer potential that can be exploited as prototype for the design of new therapies.

ACS Style

Fernanda Van Petten De Vasconcelos Azevedo; Daiana Lopes; Sarah Gimenes; David Collares Achê; Lara Vecchi; Patrícia Terra Alves; Denise De Oliveira Guimarães; Renata Santos Rodrigues; Luiz Ricardo Goulart; Veridiana De Melo Rodrigues; Kelly Aparecida Geraldo Yoneyama. Human breast cancer cell death induced by BnSP-6, a Lys-49 PLA2 homologue from Bothrops pauloensis venom. International Journal of Biological Macromolecules 2016, 82, 671 -677.

AMA Style

Fernanda Van Petten De Vasconcelos Azevedo, Daiana Lopes, Sarah Gimenes, David Collares Achê, Lara Vecchi, Patrícia Terra Alves, Denise De Oliveira Guimarães, Renata Santos Rodrigues, Luiz Ricardo Goulart, Veridiana De Melo Rodrigues, Kelly Aparecida Geraldo Yoneyama. Human breast cancer cell death induced by BnSP-6, a Lys-49 PLA2 homologue from Bothrops pauloensis venom. International Journal of Biological Macromolecules. 2016; 82 ():671-677.

Chicago/Turabian Style

Fernanda Van Petten De Vasconcelos Azevedo; Daiana Lopes; Sarah Gimenes; David Collares Achê; Lara Vecchi; Patrícia Terra Alves; Denise De Oliveira Guimarães; Renata Santos Rodrigues; Luiz Ricardo Goulart; Veridiana De Melo Rodrigues; Kelly Aparecida Geraldo Yoneyama. 2016. "Human breast cancer cell death induced by BnSP-6, a Lys-49 PLA2 homologue from Bothrops pauloensis venom." International Journal of Biological Macromolecules 82, no. : 671-677.

Review
Published: 10 March 2015 in Current Topics in Medicinal Chemistry
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Snake venoms constitute a mixture of bioactive components that are involved not only in envenomation pathophysiology but also in the development of new drugs to treat many diseases. Different enzymatic and non-enzymatic proteins, such as phospholipases A2, hyaluronidases, L-amino acid oxidases, metalloproteinases, serine proteinases, lectins and disintegrins have been isolated and their functional and structural properties described in the literature. Many of these studies have also explored their medicinal potential focusing mainly on anticancer, antithrombotic and microbicide therapies. Bothrops pauloensis is a species found in Brazil, whose venom has been the focus of our studies in order to explore the biochemical and functional characteristics of their components. In this review, we have presented the main results of years of research on different toxins from B. pauloensis emphasizing their therapeutic potential. Studies concerning snake venom toxins to search for new therapeutic models open perspectives for new drug discovery.

ACS Style

Veridiana De Melo Rodrigues; Daiana Lopes; Letícia Castanheira; Sarah Gimenes; Dayane Naves De Souza; David Ache; Isabela Borges; Kelly Yoneyama; Renata Rodrigues. Bothrops pauloensis Snake Venom Toxins: The Search for New Therapeutic Models. Current Topics in Medicinal Chemistry 2015, 15, 670 -684.

AMA Style

Veridiana De Melo Rodrigues, Daiana Lopes, Letícia Castanheira, Sarah Gimenes, Dayane Naves De Souza, David Ache, Isabela Borges, Kelly Yoneyama, Renata Rodrigues. Bothrops pauloensis Snake Venom Toxins: The Search for New Therapeutic Models. Current Topics in Medicinal Chemistry. 2015; 15 (7):670-684.

Chicago/Turabian Style

Veridiana De Melo Rodrigues; Daiana Lopes; Letícia Castanheira; Sarah Gimenes; Dayane Naves De Souza; David Ache; Isabela Borges; Kelly Yoneyama; Renata Rodrigues. 2015. "Bothrops pauloensis Snake Venom Toxins: The Search for New Therapeutic Models." Current Topics in Medicinal Chemistry 15, no. 7: 670-684.

Journal article
Published: 26 September 2014 in The Journal of Biochemistry
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We present the biochemical and functional characterization of Bothropoidin, the first haemorrhagic metalloproteinase isolated from Bothrops pauloensis snake venom. This protein was purified after three chromatographic steps on cation exchange CM-Sepharose fast flow, size-exclusion column Sephacryl S-300 and anion exchange Capto Q. Bothropoidin was homogeneous by SDS-PAGE under reducing and non-reducing conditions, and comprised a single chain of 49,558 Da according to MALDI TOF analysis. The protein presented an isoelectric point of 3.76, and the sequence of six fragments obtained by MS (MALDI TOF\TOF) showed a significant score when compared with other PIII Snake venom metalloproteinases (SVMPs). Bothropoidin showed proteolytic activity on azocasein, Aα-chain of fibrinogen, fibrin, collagen and fibronectin. The enzyme was stable at pH 6-9 and at lower temperatures when assayed on azocasein. Moreover, its activity was inhibited by EDTA, 1.10-phenanthroline and β-mercaptoethanol. Bothropoidin induced haemorrhage [minimum haemorrhagic dose (MHD) = 0.75 µg], inhibited platelet aggregation induced by collagen and ADP, and interfered with viability and cell adhesion when incubated with endothelial cells in a dose and time-dependent manner. Our results showed that Bothropoidin is a haemorrhagic metalloproteinase that can play an important role in the toxicity of B. pauloensis envenomation and might be used as a tool for studying the effects of SVMPs on haemostatic disorders and tumour metastasis.

ACS Style

M. S. R. Gomes; D. L. Naves De Souza; D. O. Guimaraes; D. S. Lopes; C. C. N. Mamede; S. N. C. Gimenes; D. C. Ache; R. S. Rodrigues; K. A. G. Yoneyama; M. H. Borges; F. De Oliveira; Veridiana De Melo Rodrigues. Biochemical and functional characterization of Bothropoidin: the first haemorrhagic metalloproteinase from Bothrops pauloensis snake venom. The Journal of Biochemistry 2014, 157, 137 -149.

AMA Style

M. S. R. Gomes, D. L. Naves De Souza, D. O. Guimaraes, D. S. Lopes, C. C. N. Mamede, S. N. C. Gimenes, D. C. Ache, R. S. Rodrigues, K. A. G. Yoneyama, M. H. Borges, F. De Oliveira, Veridiana De Melo Rodrigues. Biochemical and functional characterization of Bothropoidin: the first haemorrhagic metalloproteinase from Bothrops pauloensis snake venom. The Journal of Biochemistry. 2014; 157 (3):137-149.

Chicago/Turabian Style

M. S. R. Gomes; D. L. Naves De Souza; D. O. Guimaraes; D. S. Lopes; C. C. N. Mamede; S. N. C. Gimenes; D. C. Ache; R. S. Rodrigues; K. A. G. Yoneyama; M. H. Borges; F. De Oliveira; Veridiana De Melo Rodrigues. 2014. "Biochemical and functional characterization of Bothropoidin: the first haemorrhagic metalloproteinase from Bothrops pauloensis snake venom." The Journal of Biochemistry 157, no. 3: 137-149.

Journal article
Published: 01 April 2014 in Toxicon
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In the present work, we describe the isolation and partial structural and biochemical characterization of the first phospholipase A2 inhibitor (γPLI) from Crotalus durissus collilineatus (Cdc) snake serum. Initially, the Cdc serum was subjected to a Q-Sepharose ion exchange column, producing six peaks at 280 nm absorbance (Q1-Q6). Subsequently, Q4 fraction was submitted to affinity chromatography with immobilized PLA2 BnSP-7, a step that resulted in two fractions (NHS-1 and NHS-2). The latter contained the inhibitor, denominated γCdcPLI. The molecular mass of γCdcPLI, determined by Matrix-Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF), was 22,340 Da. Partial sequences obtained by Edman degradation and by mass spectrometry (MALDI-TOF/TOF), showed similarity, as expected, to other related inhibitors. Circular dichroism (CD) analysis showed the presence of approximately 22% alpha helices and 29% beta sheets in the protein secondary structure. Additionally, CD studies also indicated no significant changes in the secondary structure of γCdcPLI when it is complexed to BpPLA2-TXI. On the other hand, dynamic light scattering (DLS) assays showed a temperature-dependent oligomerization behavior for this inhibitor. Biochemical analyses showed γCdcPLI was able to inhibit the enzymatic, cytotoxic and myotoxic activities of PLA2s. Structural and functional studies performed on this inhibitor may elucidate the action mechanisms of PLA2 inhibitors. In addition, we hope this study may contribute to investigating the potential use of these inhibitors for the treatment of snakebite or inflammatory diseases in which PLA2s may be involved.

ACS Style

Sarah Natalie Cirilo Gimenes; Francis Barbosa Ferreira; Ana Carolina Portella Silveira; Renata Santos Rodrigues; Kelly Aparecida Geraldo Yoneyama; Juliana Izabel dos Santos; Marcos Roberto De Mattos Fontes; Vera Lúcia De Campos Brites; André Luiz Quagliatto Santos; Márcia Helena Borges; Daiana Silva Lopes; Veridiana M. Rodrigues. Isolation and biochemical characterization of a γ-type phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum. Toxicon 2014, 81, 58 -66.

AMA Style

Sarah Natalie Cirilo Gimenes, Francis Barbosa Ferreira, Ana Carolina Portella Silveira, Renata Santos Rodrigues, Kelly Aparecida Geraldo Yoneyama, Juliana Izabel dos Santos, Marcos Roberto De Mattos Fontes, Vera Lúcia De Campos Brites, André Luiz Quagliatto Santos, Márcia Helena Borges, Daiana Silva Lopes, Veridiana M. Rodrigues. Isolation and biochemical characterization of a γ-type phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum. Toxicon. 2014; 81 ():58-66.

Chicago/Turabian Style

Sarah Natalie Cirilo Gimenes; Francis Barbosa Ferreira; Ana Carolina Portella Silveira; Renata Santos Rodrigues; Kelly Aparecida Geraldo Yoneyama; Juliana Izabel dos Santos; Marcos Roberto De Mattos Fontes; Vera Lúcia De Campos Brites; André Luiz Quagliatto Santos; Márcia Helena Borges; Daiana Silva Lopes; Veridiana M. Rodrigues. 2014. "Isolation and biochemical characterization of a γ-type phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum." Toxicon 81, no. : 58-66.

Journal article
Published: 04 December 2013 in Toxins
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In this work, we describe the molecular cloning and pharmacological properties of an acidic phospholipase A2 (PLA2) isolated from Bothrops pauloensis snake venom. This enzyme, denominated BpPLA2-TXI, was purified by four chromatographic steps and represents 2.4% of the total snake venom protein content. BpPLA2-TXI is a monomeric protein with a molecular mass of 13.6 kDa, as demonstrated by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) analysis and its theoretical isoelectric point was 4.98. BpPLA2-TXI was catalytically active and showed some pharmacological effects such as inhibition of platelet aggregation induced by collagen or ADP and also induced edema and myotoxicity. BpPLA2-TXI displayed low cytotoxicity on TG-180 (CCRF S 180 II) and Ovarian Carcinoma (OVCAR-3), whereas no cytotoxicity was found in regard to MEF (Mouse Embryonic Fibroblast) and Sarcoma 180 (TIB-66). The N-terminal sequence of forty-eight amino acid residues was determined by Edman degradation. In addition, the complete primary structure of 122 amino acids was deduced by cDNA from the total RNA of the venom gland using specific primers, and it was significantly similar to other acidic D49 PLA2s. The phylogenetic analyses showed that BpPLA2-TXI forms a group with other acidic D49 PLA2s from the gender Bothrops, which are characterized by a catalytic activity associated with anti-platelet effects.

ACS Style

Francis Barbosa Ferreira; Mário Sérgio Rocha Gomes; Dayane Lorena Naves De Souza; Sarah Natalie Cirilo Gimenes; Letícia Eulalio Castanheira; Márcia Helena Borges; Renata Santos Rodrigues; Kelly Aparecida Geraldo Yoneyama; Maria Inês Homsi Brandeburgo; Veridiana M. Rodrigues. Molecular Cloning and Pharmacological Properties of an Acidic PLA2 from Bothrops pauloensis Snake Venom. Toxins 2013, 5, 2403 -2419.

AMA Style

Francis Barbosa Ferreira, Mário Sérgio Rocha Gomes, Dayane Lorena Naves De Souza, Sarah Natalie Cirilo Gimenes, Letícia Eulalio Castanheira, Márcia Helena Borges, Renata Santos Rodrigues, Kelly Aparecida Geraldo Yoneyama, Maria Inês Homsi Brandeburgo, Veridiana M. Rodrigues. Molecular Cloning and Pharmacological Properties of an Acidic PLA2 from Bothrops pauloensis Snake Venom. Toxins. 2013; 5 (12):2403-2419.

Chicago/Turabian Style

Francis Barbosa Ferreira; Mário Sérgio Rocha Gomes; Dayane Lorena Naves De Souza; Sarah Natalie Cirilo Gimenes; Letícia Eulalio Castanheira; Márcia Helena Borges; Renata Santos Rodrigues; Kelly Aparecida Geraldo Yoneyama; Maria Inês Homsi Brandeburgo; Veridiana M. Rodrigues. 2013. "Molecular Cloning and Pharmacological Properties of an Acidic PLA2 from Bothrops pauloensis Snake Venom." Toxins 5, no. 12: 2403-2419.