Analysis of the effects and mechanisms of the Phoneutria nigriventer spider venom on morphology and migration of tumor cells

• Grant number: 17/16196-2
• Support type: Scholarships in Brazil - Master
• Effective date (Start): September 01, 2017
• Effective date (End): August 31, 2019
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal researcher: Catarina Raposo Dias Carneiro
• Grantee: Natália Barreto dos Santos
• Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 15/04194-0 - Identification of new molecules with chemotherapeutic effect in human glioma and characterization of the mechanism, AP.JP

Abstract

Malignant gliomas are brain tumors originating from glial cells, mainly of astrocytes. It is a devastating human cancer, whose incidence and mortality are expected to increase in the coming years. The intense cell migration, which results in the high capacity to invade healthy nervous tissue, is one of the characteristics of gliomas that makes its treatment difficult. The RhoA/ROCK pathway regulates the cytoskeleton, cell morphology and motility, and mutations in this pathway are related to tumor cell migration and invasion. In addition, altered expression of matrix metalloproteinases (MMPs) is a common finding in gliomas, increasing the proteolysis of the extracellular matrix and, consequently, facilitating cell invasion and the occurrence of metastases. Finding molecules that regulate not only survival and proliferation but also the migration and invasion of tumor cells, is one of the major challenges in anticancer pharmacology. Animal poisons are a mixture of biologically active molecules with specific targets in cells and tissues. The venom of the Phoneutria nigriventer (PNV) spider (Ctenidae, Araneomorpha) contains potent basic peptides, some of them neurotoxic. It has recently been demonstrated by our group that astrocytes are directly target by molecules present in the venom. In astrocyte primary culture, PNV evoked transient Ca 2+ waves in a dose-dependent manner, altered the actin cytoskeleton (stress fibers), balance between F- and G-actin and modified cell morphology. Despite these relevant changes in cytoskeleton and morphology, it has not yet been investigated whether the PNV and its components would have effects on cell migration, invasion and metastasis in gliomas. The present work aims to investigate the antitumor role of PNV in vitro in glioma cell lines (NG97ht), glioblastoma (U87MG) and cervical tumor (HeLa), describing the effects of venom and its purified peptide on the cytoskeleton, migration and tumor cell morphology. In order to contribute to elucidate the mechanism of action of PNV, the RhoA/ROCK pathway and matrix metalloproteinases (MMP-2 and MMP-9) will be evaluated. The study will be conducted through morphological and molecular methods and will contribute to the development of new potential treatments for brain tumor. (AU)

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)

BARRETO, NATALIA; CABALLERO, MARCUS; BONFANTI, AMANDA PIRES; PINHEIRO DE MATO, FELIPE CEZAR; MUNHOZ, JAQUELINE; DA ROCHA-E-SILVA, THOMAZ A. A.; SUTTI, RAFAEL; VITORINO-ARAUJO, JOAO LUIZ; VERINAUD, LIANA; RAPOSO, CATARINA. Spider venom components decrease glioblastoma cell migration and invasion through RhoA-ROCK and Na+/K+-ATPase beta 2: potential molecular entities to treat invasive brain cancer. CANCER CELL INTERNATIONAL, v. 20, n. 1 DEC 17 2020. Web of Science Citations: 0.

BONFANTI, AMANDA PIRES; BARRETO, NATALIA; MUNHOZ, JAQUELINE; CABALLERO, MARCUS; CORDEIRO, GABRIEL; ROCHA-E-SILVA, THOMAZ; SUTTI, RAFAEL; MOURA, FERNANDA; BRUNETTO, SERGIO; RAMOS, CELSO DARIO; THOME, RODOLFO; VERINAUD, LIANA; RAPOSO, CATARINA. Spider venom administration impairs glioblastoma growth and modulates immune response in a non-clinical model. SCIENTIFIC REPORTS, v. 10, n. 1 APR 3 2020. Web of Science Citations: 1.

DOS SANTOS, NATALIA BARRETO; BONFANTI, AMANDA PIRES; ALVES DA ROCHA-E-SILVA, THOMAZ AUGUSTO; DA SILVA, JR., PEDRO ISMAEL; DA CRUZ-HOFLING, MARIA ALICE; VERINAUD, LIANA; RAPOSO, CATARINA. Venom of the Phoneutria nigriventer spider alters the cell cycle, viability, and migration of cancer cells. Journal of Cellular Physiology, v. 234, n. 2, p. 1398-1415, FEB 2019. Web of Science Citations: 1.