Investigation of mechanisms of action of the lectin BfL (Bauhinia forficata) in tumor cell lines: relation between structure and specificity.

• Grant number: 12/06366-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2012
• End date: November 30, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Maria Luiza Vilela Oliva
• Grantee: Mariana Cristina Cabral Silva
• Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 09/53766-5 - 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, AP.TEM
• Associated scholarship(s): 14/22649-1 - Determination of the crystal structure of the lectin BfL (Bauhinia forficata) and the effect of this protein, as well the protease inhibitors EcTI (Enterolobium contortisiliquum) and CrataBL (Crataeva tapia) on the NCI-60 cell line panel, BE.EP.PD

Abstract

Lectins are proteins or glycoproteins, that have at least one non-catalytic domain, able to reversibly bind to specific monosaccharides or oligosaccharides without changing their properties. Glycoproteins play important functions, and due to their ability to discriminate carbohydrate structures, they have been used in the diagnosis to differentiate malignant and benign tumors, and the degree of glycosylation associated with metastases. As tumor cells express different glycoconjugates in their membranes, new potential biomarkers of cancer are investigated. During the doctoral of the candidate it was characterized the structure of a lectin (glycoprotein) isolated from Bauhinia forficata (Silva et al., 2012), which belongs to the Leguminosae family, and the preliminary results indicate the promising action of this lectin, named BfL, on breast cancer line MCF-7. Apart from inhibition of cell viability, BfL promoted mitochondrial cell death, nuclear DNA fragmentation with consequent cell cycle arrest in the G2/M phase, and inhibition of adhesion of these cells to adhesion molecules by affecting the expression of ±6 and ²1 integrins. These findings indicate that the protein structure displays unique characteristics and the knowledge of the regions responsible for such effects may result in the development of low molecular weight compounds with antitumor activity and assist in the knowledge of the mechanisms that activate the cell death pathways triggered by the lectin.

Scientific publications

(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)

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)

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)