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Study of the endothelial regenerative ability of the secondary metabolite annularin produced by the fungal Exserohilum rostratum

Grant number: 14/19152-8
Support Opportunities:Regular Research Grants
Start date: December 01, 2014
End date: November 30, 2016
Field of knowledge:Health Sciences - Pharmacy - Pharmacognosy
Principal Investigator:Ana Olívia de Souza
Grantee:Ana Olívia de Souza
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Anularin FV3 is a secondary metabolite obtained from fungal Exserohilum rostratum, which failed to show in vitro antitumoral activity in the tumoral cell lines K-562 (human leukemia) and on B16F10 (murine melanome). However, this compound induced proliferation of the human umbilical vein endothelial cells (HUVECs) that was five times higher than in the control group. Based on this observation the aim of this current study focuses on the cellular proliferation induced by anularin FV3. This will be done using models of the cellular strains of HUVEC and normal human fibroblasts (FN1). The results of this study will have a broad impact for future use in tissue regeneration and remodeling. The effects of anularin FV3 treatment will be studied; 1) in the cellular cycle phase using flow cytometer, (2) in the expression of regulators of the receptors from the cellular cycle, and (3) in the 3D formation in organotypic culture system of the endothelial vessel and ramifications. More robust and specific techniques as "Real-Time PCR" and "Western blot" will be applied for confirmation.Understanding the mechanisms of cellular proliferation and regeneration induced by anularin FV3, and its influence in the signaling pathways that control the cell cycle progression in HUVEC and FN1 cells will be an important contribution in tissue regeneration and medicine. This approach represents an innovative and novel possibility of biotecnological applications of fungal E. rostratum, specifically using the secondary metabolites such as, anularin FV3. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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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)
GOMES, TAINAH COLOMBO; CONRADO, RAFAEL; DE OLIVEIRA, RODRIGO CARDOSO; SELARI, PRISCILA JANE ROMANO GONCALVES; DE MELO, ITAMAR SOARES; ARAUJO, WELINGTON LUIZ; MARIA, DURVANEI AUGUSTO; DE SOUZA, ANA OLIVIA. Effect of Monocerin, a Fungal Secondary Metabolite, on Endothelial Cells. TOXINS, v. 15, n. 5, p. 18-pg., . (14/19152-8, 17/26524-7)