Journal
GENETICS AND MOLECULAR BIOLOGY
Volume 43, Issue 3, Pages -Publisher
SOC BRASIL GENETICA
DOI: 10.1590/1678-4685-GMB-2019-0347
Keywords
Polyphenols; comet assay; micronucleus; neutral red
Funding
- Sao Paulo Research Foundation (FAPESP) [2013/13733-6]
- National Council for Scientific and Technological Development (CNPq) [302290/2015-0]
- Coordination for the Improvement of Higher Education Personnel (CAPES) [001]
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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 mu M) 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 mu M) 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 mu M) 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.
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