Caffeic acid and chlorogenic acid cytotoxicity, genotoxicity and impact on global DNA methylation in human leukemic cell lines

Author(s)

Lívia Cristina Hernandes ^[1] ; Ana Rita Thomazela Machado ^[2] ; Katiuska Tuttis ^[3] ; Diego Luís Ribeiro ^[4] ; Alexandre Ferro Aissa ^[5] ; Paula Pícoli Dévoz ^[6] ; Lusânia Maria Greggi Antunes ^[7]

Affiliation

^[1] Universidade de São Paulo - USP. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Brasil

^[2] Universidade de São Paulo - USP. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Brasil

^[3] Universidade de São Paulo USP. Faculdade de Medicina de Ribeirão Preto - Brasil

^[4] Universidade de São Paulo USP. Faculdade de Medicina de Ribeirão Preto - Brasil

^[5] Universidade de São Paulo - USP. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Brasil

^[6] Universidade de São Paulo - USP. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Brasil

^[7] Universidade de São Paulo - USP. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Brasil

• Document type: Journal article
• Source: GENETICS AND MOLECULAR BIOLOGY; v. 43, n. 3 2020-07-03.

Abstract

Abstract Dietary phenolic compounds such as caffeic and chlorogenic acid exert an antiproliferative effect and modulate the gene-specific DNA methylation status in human breast tumor cells, but it remains unclear whether they interfere with global DNA methylation in human leukemia cells. We examined whether caffeic and chlorogenic acid (1-250 µM) exert antitumor action in human promyelocytic leukemia cells (HL-60) and human acute T-cell leukemia cells (Jurkat). Caffeic and chlorogenic acid did not reduce cell viability in the two cell lines, as assessed using the neutral red uptake and MTT assays. These phenolic acids (1-100 μM) neither induced DNA damage (comet assay) nor increased the micronuclei frequency (micronucleus assay) in HL-60 and Jurkat cells, indicating that they were not genotoxic or mutagenic. Analysis of global DNA methylation levels using a 5-mC DNA ELISA kit revealed that chlorogenic acid at a non-cytotoxic concentration (100 μM) induced global DNA hypomethylation in Jurkat cells, but not in HL-60 cells, suggesting that it exerts a cell-specific effect. Caffeic acid did not change global DNA methylation. As other phenolic compounds, chlorogenic acid probably modulates DNA methylation by targeting DNA methyltransferases. The hypomethylating action of chlorogenic acid can be beneficial against hematological malignances whose pathogenic processes involve impairment of DNA methylation. (AU)

• FAPESP's process: 13/13733-6 - Comparison of caffeic and chlorogenic acids effects on methylation, cytotoxicity, genotoxicity and gene expression on human cells Jurkat, HL-60 and JMA exposed to 5-azacytidine demethylating agent
• Grantee: Lívia Cristina Hernandes
• Support Opportunities: Scholarships in Brazil - Doctorate