Analysis of the mechanisms by which polyphenols epigallocatechin 3 gallate and Quercetin modulate epigenetic alterations present in leukemias and myelodysplastic syndromes

• Grant number: 15/21164-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2016
• End date: June 30, 2020
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Sara Teresinha Olalla Saad
• Grantee: Marisa Claudia Alvarez de Prax
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/21801-2 - Predictors of severity and new treatments for bone marrow neoplasias, AP.TEM

Abstract

Epigenetic changes play a crucial role in hematological malignancies, and as they are reversible constitute an important therapeutic target. This characteristic not only increased the search of new synthesized drugs but also increased the interest on the diet-derived compounds with chemopreventive and therapeutic properties. Recent published results of our group, showed that Quercetin (Qu) in vitro and in vivo (xenotransplant) has anti proliferative effect, activates the autophagy pathway and induces apoptosis upregulating the pro apoptotic protein BAX, and through downregulation of BCL2 and MCL-1C proteins levels. Regarding epigenetics modifications (paper in process of submission), we observed that Qu induced demethylation of the promoter region of pro-apoptotic BCL2L11, DAPK1 genes, and dose and time dependent. Qu up-regulated the expression profile of 63% (n=17) and 24% (n=4) (in vitro and in vivo, respectively) of the miRNAs evaluated. Of these, 42% (n=7) and 100% (n=4) corresponded exclusively to miRNAs that target anti-apoptotic genes and to miRNAs that have been demonstrated to have pro-apoptotic functions. Moreover, Qu increased to 2-15 folds histone 3(H3ac) and 4(H4ac) acetylation in the promoter region of 96% (n=80) of the genes evaluated. Taking these into account, we aimed to investigate the mechanisms by which Qu has the capacity to modify epigenetic alterations in myelodysplastic syndromes and leukemia and also analyze the principal constituent of Green tea, Epigallocathechin 3 gallate, for its capacity as epigenetic modifier.

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)

ALVAREZ, MARISA CLAUDIA; MASO, VICTOR; TORELLO, CRISTIANE OKUDA; FERRO, KARLA PRISCILLA; OLALLA SAAD, SARA TERESINHA. The polyphenol quercetin induces cell death in leukemia by targeting epigenetic regulators of pro-apoptotic genes. CLINICAL EPIGENETICS, v. 10, NOV 8 2018. (15/21164-7)