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Vol. 44. Núm. S2.
Páginas S649 (outubro 2022)
Vol. 44. Núm. S2.
Páginas S649 (outubro 2022)
Open Access
METABOLOMIC PROFILING OF THE POLYPHENOL QUERCETIN RESPONSE IN LEUKEMIA CELL LINES
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MC Alvareza,b, TB Costac, L Tasicc, STO Saada,b
a Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brasil
b Centro de Hematologia e Hemoterapia (Hemocentro), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brasil
c Institute of Chemistry, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brasil
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Epigenetic changes play a crucial role in hematological malignancies and the protein network that regulates these mechanisms offers potential pharmacologic regulation. Flavonoids might exert antitumoral effects through induction of apoptosis and chromatin remodeling. Our previous study showed that Quercetin (Qu) induced apoptosis, partly due to its DNA demethylating activity, through HDAC inhibition and enrichment of H3ac and H4ac in the promoter regions of the genes involved in the apoptosis pathway, leading to their transcription activation (Alvarez, Clinical Epigenetics 2018). The 1H NMR spectra of the aqueous extract of exponentially growing HL-60 and U937 cell lines untreated and treated with Qu (50 mM, 48h) were obtained and analyzed by Principal Component Analysis (PCA). PCA revealed discrimination between the intracellular metabolome of the cell lines regarding Qu treatment. The subtraction of the mean 1H NMR spectra of each treated and untreated cell line, as well as the PCA loadings, identified as major discriminators in HL-60 cell line, lactate, alanine, acetate, phosphocholine, taurine, glycine, glutamate and myo-inositol. Lactate was elevated in Qu treated cells whereas the other metabolites were decreased compared to control cells. For the U937 cell line, the major discriminators were the same, with the addition of creatine and the exclusion of lactate. All of them were decreased in treated samples. It could be concluded that Qu induced intracellular lactate accumulation in the HL-60 cell line, contributing to apoptosis induction. Acetate and N-acetyl groups levels were decreased in treated cells, which is consistent with our previous results as Qu treatment induced H3 and H4 acetylation that may induce an increase in acetyl-CoA consumption. In summary, the data presented pointed to metabolic changes measurable by NMR induced by Qu in AMLs cell lines and reflect the direct connection between metabolism and chromatin dynamics.

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Hematology, Transfusion and Cell Therapy
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