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Investigation of the cytotoxic/apoptotic potential of new flavonoid derivatives: in vitro and in vivo studies

Grant number: 12/04634-1
Support type:Regular Research Grants
Duration: July 01, 2012 - December 31, 2014
Field of knowledge:Health Sciences - Nutrition
Principal Investigator:Denise Gonçalves Priolli
Grantee:Denise Gonçalves Priolli
Home Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil
Assoc. researchers:Patrícia de Oliveira Carvalho
Associated scholarship(s):12/18851-4 - Investigation of the cytotoxic/apoptotic potential of new flavonoid derivatives: in vitro and in vivo studies, BP.TT

Abstract

Flavonoids are one of the most important and diversified groups of phenolic compounds of natural origin. Various biological activities, including their anti-tumor, antioxidant, antiviral and anti-inflammatory effects, are attributed to this class of polyphenols, endowing them with great pharmacological importance. This project sets out to evaluate new flavonoid compounds obtained from hesperidin, naringin and rutin and their aglycone structural correspondents by means of acylating (lipases) and deglycosilating (rhamnosidases and glycosidases) reactions, and particularly to evaluate: 1) their cytotoxic activity in vitro using lines of cancer cells: lung/NCI-H460; breast/MCF-7; ovary/OVCAR-3; resistant ovary/NCI-ADR/Res; colon/HT-29; prostate/PC-3; melanoma/UACC-62; renal/786-0 and leukemia/K-562; 2) their therapeutic activity in an animal model of human adenocarcinomas in athimic mice. The biotransformation reactions will be monitored by mass spectrometry (ESI-MS)). Immunohistochemistry will be used to evaluate the expression of the p53, ING2 and VEGF, quantifying the apoptotic response (p53) and the cellular proliferation (ING2) and angiogenesis (VEGF ) responses. The therapeutic effects will be assessed by cytotoxicity and flow cytometry tests. The working proposal is based on preliminary results obtained with bio-transformed flavonoids showing high antioxidant potential. The aim is to elucidate the characteristic structures within these compounds and their relation to their anti-cancer activity. The team is made up of researchers with wide experience in the fields of Pharmacology, Oncology and Foodstuffs as well as graduate and post-graduate students. The proposed bio-technological processes are unprecedented and may well give rise to new functional compounds and foster an expansion of knowledge on their structure/activity relationships and it action by heterologous transplantatios of colon adenocarcinoma in vivo. (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)
PARISI DE OLIVEIRA, CARLOS TADEU; COLENCI, RENATO; PACHECO, CESAR COZAR; MARIANO, PATRICK MORO; DO PRADO, PAULA RIBEIRO; ROSAS MAMPRIN, GUSTAVO PIGNATARI; SANTANA, MAYCON GIOVANI; GAMBERO, ALESSANDRA; CARVALHO, PATRICIA DE OLIVEIRA; PRIOLLI, DENISE GONCALVES. Hydrolyzed Rutin Decreases Worsening of Anaplasia in Glioblastoma Relapse. CNS & Neurological Disorders-Drug Targets, v. 18, n. 5, p. 405-412, 2019. Web of Science Citations: 1.
DE MIGUEL, GUILHERME CHOHFI; ABRANTES, ANA MARGARIDA; LARANJO, MAFALDA; KITAGAWA GRIZOTTO, ANA YOSHIE; CAMPOREZE, BRUNO; PEREIRA, JOSE AIRES; BRITES, GONCALO; SERRA, ARMENIO; PINEIRO, MARTA; ROCHA-GONSALVES, ANTONIO; BOTELHO, MARIA FILOMENA; PRIOLLI, DENISE GONCALVES. A new therapeutic proposal for inoperable osteosarcoma: Photodynamic therapy. Photodiagnosis and Photodynamic Therapy, v. 21, p. 79-85, MAR 2018. Web of Science Citations: 2.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.