Proteins from plant source with selectivity for inhibition of mammalian enzymes and their role as an anti-inflammatory, antithrombotic, anti-diabetic and anti-tumor agent

• Grant number: 09/53766-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: March 01, 2010
• End date: February 29, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Maria Luiza Vilela Oliva
• Grantee: Maria Luiza Vilela Oliva
• Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Pesquisadores principais: Francisco Humberto de Abreu Maffei
• Associated scholarship(s): 13/13239-1 - Study of the mechanism of action of the protease inhibitor EcTI and structurally related synthetic peptides on human leukemic cell lines., BP.PD; 14/04178-1 - Role of peptides in coagulation and platelet aggregation, BP.IC; 12/06366-4 - Investigation of mechanisms of action of the lectin BfL (Bauhinia forficata) in tumor cell lines: relation between structure and specificity., BP.PD; 10/19045-6 - Study of Antiangiogenic Potential of Proteases Inhibitors Isolated from Brazilian Plants., BP.IC

Abstract

Proteins obtained from seeds of Brazilian plants with inhibitory function on different classes of proteolytic enzymes, on coagulation factors and fibrinolysis, on platelet aggregation were characterized. The inhibitors of coagulation factors and antagonists of platelet activation can be considered for the development of anti-thrombotic drugs. Others inhibit the adhesion of tumor cells to extracellular matrix and apoptosis, thus suggesting a strong potential as anti-metastatic agents or for prevention of ischemia-reperfusion syndrome and others have hypoglycemic action. Major structural differences between the inhibitors might be significant for the specificity and mechanism of action that this study proposes to clarify. This knowledge may contribute to clarify the physiopathology of diseases and to develop compounds that could be applied as tools for diagnostic or therapeutic use. (AU)

Scientific publications

(21)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZHOU, DONGWEN; HANSEN, DAIANE; SHABALIN, IVAN G.; GUSTCHINA, ALLA; VIEIRA, DEBORA F.; DE BRITO, MARLON V.; ARAUJO, ANA PAULA U.; OLIVA, MARIA LUIZA V.; WLODAWER, ALEXANDER. Structure of BbKI, a disulfide-free plasma kallikrein inhibitor. ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, v. 71, n. 8, p. 1055-1062, AUG 2015. (09/53766-5)

LUBKOWSKI, JACEK; DURBIN, SARAH V.; SILVA, MARIANA C. C.; FARNSWORTH, DAVID; GILDERSLEEVE, JEFFREY C.; OLIVA, MARIA LUIZA V.; WLODAWER, ALEXANDER. Structural analysis and unique molecular recognition properties of a Bauhinia forficata lectin that inhibits cancer cell growth. FEBS Journal, v. 284, n. 3, p. 429-450, FEB 2017. (12/06366-4, 14/22649-1, 09/53766-5)

OTTAIANO, TATIANA F.; ANDRADE, SHEILA S.; DE OLIVEIRA, CLEIDE; SILVA, MARIANA C. C.; BURI, MARCUS V.; JULIANO, MARIA A.; GIRAO, MANOEL J. B. C.; SAMPAIO, MISAKO U.; SCHMAIER, ALVIN H.; WLODAWER, ALEXANDER; et al. Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP. Biochimie, v. 135, p. 72-81, APR 2017. (12/19780-3, 09/53766-5)

BONAZZA, CAMILA; ANDRADE, SHEILA SIQUEIRA; SUMIKAWA, JOANA TOMOMI; BATISTA, FABRICIO PEREIRA; PAREDES-GAMERO, EDGAR J.; GIRAO, MANOEL J. B. C.; OLIVA, MARIA LUIZA V.; CASTRO, RODRIGO AQUINO. Primary Human Uterine Leiomyoma Cell Culture Quality Control: Some Properties of Myometrial Cells Cultured under Serum Deprivation Conditions in the Presence of Ovarian Steroids. PLoS One, v. 11, n. 7, JUL 8 2016. (12/19851-8, 09/53766-5, 12/19780-3)

SALU, BRUNO R.; FERREIRA, RODRIGO S.; BRITO, MARLON V.; OTTAIANO, TATIANA F.; CRUZ, JOSE WALBER M. C.; SILVA, MARIANA CRISTINA C.; CORREIA, MARIA TEREZA S.; PAIVA, PATRICIA M. G.; MAFFEI, FRANCISCO HUMBERTO A.; VILELA OLIVA, MARIA LUIZA. CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation. Biological Chemistry, v. 395, n. 9, p. 1027-1035, SEP 2014. (09/53766-5)

BRITO, MARLON V.; DE OLIVEIRA, CLEIDE; SALU, BRUNO R.; ANDRADE, SONIA A.; MALLOY, PAULA M. D.; SATO, ANA C.; VICENTE, CRISTINA P.; SAMPAIO, MISAKO U.; MAFFEI, FRANCISCO H. A.; OLIVA, MARIA LUIZA V.. The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models. THROMBOSIS RESEARCH, v. 133, n. 5, p. 945-951, MAY 2014. (09/53766-5, 12/23640-2)

ANDRADE DE PAULA, CLAUDIA ALESSANDRA; COULSON-THOMAS, VIVIEN JANE; FERREIRA, JOANA GASPERAZZO; MAZA, PALOMA KOREHISA; SUZUKI, ERIKA; NAKAHATA, ADRIANA MITI; NADER, HELENA BONCIANI; SAMPAIO, MISAKO UEMURA; OLIVA, MARIA LUIZA V.. Enterolobium contortisiliquum Trypsin Inhibitor (EcTI), a Plant Proteinase Inhibitor, Decreases in Vitro Cell Adhesion and Invasion by Inhibition of Src Protein-Focal Adhesion Kinase (FAK) Signaling Pathways. Journal of Biological Chemistry, v. 287, n. 1, p. 170-182, JAN 2 2012. (09/53766-5)

ZHOU, DONGWEN; LOBO, YARA A.; BATISTA, ISABEL F. C.; MARQUES-PORTO, RAFAEL; GUSTCHINA, ALLA; OLIVA, MARIA L. V.; WLODAWER, ALEXANDER. Crystal Structures of a Plant Trypsin Inhibitor from Enterolobium contortisiliquum (EcTI) and of Its Complex with Bovine Trypsin. PLoS One, v. 8, n. 4, APR 23 2013. (09/53766-5)

ZHANG, FUMING; WALCOTT, BENJAMIN; ZHOU, DONGWEN; GUSTCHINA, ALLA; LASANAJAK, YI; SMITH, DAVID F.; FERREIRA, RODRIGO S.; CORREIA, MARIA TEREZA S.; PAIVA, PATRICIA M. G.; BOVIN, NICOLAI V.; et al. Structural Studies of the Interaction of Crataeva tapia Bark Protein with Heparin and Other Glycosaminoglycans. BIOCHEMISTRY, v. 52, n. 12, p. 2148-2156, MAR 26 2013. (09/53766-5)

NAKAHATA, ADRIANA MITI; MAYER, BARBARA; NETH, PETER; HANSEN, DAIANE; SAMPAIO, MISAKO UEMURA; VILELA OLIVA, MARIA LUIZA. Blocking the Proliferation of Human Tumor Cell Lines by Peptidase Inhibitors from Bauhinia Seeds. Planta Medica, v. 79, n. 3-4, p. 227-235, MAR 2013. (09/53766-5)

SILVA, MARIANA C. C.; SANTANA, LUCIMEIRE A.; MENTELE, REINHARD; FERREIRA, RODRIGO S.; DE MIRANDA, ANTONIO; SILVA-LUCCA, ROSEMEIRE A.; SAMPAIO, MISAKO U.; CORREIA, MARIA T. S.; OLIVA, MARIA L. V.. Purification, primary structure and potential functions of a novel lectin from Bauhinia forficata seeds. Process Biochemistry, v. 47, n. 7, p. 1049-1059, JUL 2012. (09/53766-5)

ZHOU, DONGWEN; HANSEN, DAIANE; SHABALIN, IVAN G.; GUSTCHINA, ALLA; VIEIRA, DEBORA F.; DE BRITO, MARLON V.; ARAUJO, ANA PAULA U.; OLIVA, MARIA LUIZA V.; WLODAWER, ALEXANDER. Structure of BbKI, a disulfide-free plasma kallikrein inhibitor. ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, v. 71, p. 8-pg., 2015-08-01. (09/53766-5)

ANDRADE, SHEILA SIQUEIRA; SUMIKAWA, JOANA TOMOMI; CASTRO, ELOISA DOGNANI; BATISTA, FABRICIO PEREIRA; PAREDES-GAMERO, EDGAR; OLIVEIRA, LILIAN CAROLINA; GUERRA, IZABEL MONASTERIO; PERES, GIOVANI BRAVIN; CAVALHEIRO, RENAN PELLUZZI; JULIANO, LUIZ; et al. Interface between breast cancer cells and the tumor microenvironment using platelet-rich plasma to promote tumor angiogenesis - influence of platelets and fibrin bundles on the behavior of breast tumor cells. ONCOTARGET, v. 8, n. 10, p. 16851-16874, 2017. (12/19851-8, 09/53766-5, 12/19780-3)

OLIVA, LEANDRO V.; ALMEIDA-REIS, RAFAEL; THEODORO-JUNIOR, OSMAR; OLIVEIRA, BRUNO M.; LEICK, EDNA A.; PRADO, CARLA M.; BRITO, MARLON V.; DOS SANTOS CORREIA, MARIA TEREZA; PAIVA, PATRICIA M. G.; MARTINS, MILTON A.; et al. A plant proteinase inhibitor from Crataeva tapia (CrataBL) attenuates elastase-induced pulmonary inflammatory, remodeling, and mechanical alterations in mice. Process Biochemistry, v. 50, n. 11, p. 1958-1965, NOV 2015. (11/01165-8, 09/53766-5)

NUNES, NATALIA N. S.; FERREIRA, RODRIGO S.; SILVA-LUCCA, ROSEMEIRE A.; DE SA, LEONARDO F. R.; DE OLIVEIRA, ANTONIA ELENIR A.; CORREIA, MARIA TEREZA DOS S.; PAIVA, PATRICIA MARIA G.; WLODAWER, ALEXANDER; OLIVA, MARIA LUIZA V.. Potential of the Lectin/Inhibitor Isolated from Crataeva tapia Bark (CrataBL) for Controlling Callosobruchus maculatus Larva Development. Journal of Agricultural and Food Chemistry, v. 63, n. 48, p. 10431-10436, DEC 9 2015. (09/17058-6, 09/53766-5)

ANDRADE, SHEILA SIQUEIRA; GOUVEA, IURI ESTRADA; SILVA, MARIANA CRISTINA C.; CASTRO, ELOISA DOGNANI; DE PAULA, CLAUDIA A. A.; OKAMOTO, DEBORA; OLIVEIRA, LILIAN; PERES, GIOVANI BRAVIN; OTTAIANO, TATIANA; FACINA, GIL; et al. Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer. BMC CANCER, v. 16, MAR 1 2016. (12/19851-8, 09/53766-5, 12/19780-3)

FERREIRA, JOANA GASPERAZZO; MOTTA DINIZ, PAULA MALLOY; ANDRADE DE PAULA, CLAUDIA ALESSANDRA; LOBO, YARA APARECIDA; PAREDES-GAMERO, EDGAR JULIAN; PASCHOALIN, THAYSA; NOGUEIRA-PEDRO, AMANDA; MAZA, PALOMA KOREHISA; TOLEDO, MARCOS SERGIO; SUZUKI, ERIKA; et al. The Impaired Viability of Prostate Cancer Cell Lines by the Recombinant Plant Kallikrein Inhibitor. Journal of Biological Chemistry, v. 288, n. 19, p. 13641-13654, MAY 10 2013. (09/53766-5)

NUNES, NATALIA N. DOS S.; SANTANA, LUCIMEIRE A.; SAMPAIO, MISAKO U.; LEMOS, FRANCISCO J. A.; OLIVA, MARIA LUIZA. The component of Carica papaya seed toxic to A-aegypti and the identification of tegupain, the enzyme that generates it. Chemosphere, v. 92, n. 4, p. 413-420, JUL 2013. (09/17058-6, 09/53766-5)

FERREIRA, RODRIGO DA SILVA; ZHOU, DONGWEN; FERREIRA, JOANA GASPERAZZO; CABRAL SILVA, MARIANA CRISTINA; SILVA-LUCCA, ROSEMEIRE APARECIDA; MENTELE, REINHARD; PAREDES-GAMERO, EDGAR JULIAN; BERTOLIN, THIAGO CARLOS; DOS SANTOS CORREIA, MARIA TEREZA; GUEDES PAIVA, PATRICIA MARIA; et al. Crystal Structure of Crataeva tapia Bark Protein (CrataBL) and Its Effect in Human Prostate Cancer Cell Lines. PLoS One, v. 8, n. 6, JUN 18 2013. (09/53766-5)

SILVA, MARIANA C. C.; DE PAULA, CLAUDIA A. A.; FERREIRA, JOANA G.; PAREDES-GAMERO, EDGAR J.; VAZ, ANGELA M. S. F.; SAMPAIO, MISAKO U.; CORREIA, MARIA TEREZA S.; OLIVA, MARIA LUIZA V.. Bauhinia forficata lectin (BfL) induces cell death and inhibits integrin-mediated adhesion on MCF7 human breast cancer cells. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1840, n. 7, p. 2262-2271, JUL 2014. (12/06366-4, 09/53766-5)

LUBKOWSKI, JACEK; DURBIN, SARAH V.; SILVA, MARIANA C. C.; FARNSWORTH, DAVID; GILDERSLEEVE, JEFFREY C.; OLIVA, MARIA LUIZA V.; WLODAWER, ALEXANDER. Structural analysis and unique molecular recognition properties of a Bauhinia forficata lectin that inhibits cancer cell growth. FEBS Journal, v. 284, n. 3, p. 22-pg., 2017-02-01. (12/06366-4, 14/22649-1, 09/53766-5)