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Study of the TRAIL-sensitizing mechanism of action of marine natural products

Grant number: 20/01125-5
Support type:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): November 01, 2021
Effective date (End): April 30, 2022
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal researcher:Leticia Veras Costa Lotufo
Grantee:Larissa Costa de Almeida
Supervisor abroad: Hendrik Luesch
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University of Florida, Gainesville (UF), United States  
Associated to the scholarship:18/17595-0 - Study of pradimicina-IRD molecular interaction with DNA and its tumor cell mechanism of action, BP.DD

Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent anticancer agent, since it can preferentially induce apoptosis in tumor cells, while sparing normal cells. TRAIL death receptors (DR5 and DR4) signal apoptosis through caspases and activate NF-kB, STAT-3, p38, ERK1/2, and JNK pathways. The aim of this study is to evaluate the TRAIL-sensitizing natural products, which shows the potential cytotoxic activity in the presence of TRAIL, but not in the absence of it. Additionally, we propose to understand the TRAIL-sensitizing mechanism of action of the compounds, underlying DR4 and DR5 transcription induction, expression and localization, DR4 and DR5 downstream pathways, and ligand (natural products) and target interactions. (AU)

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