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

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 mM) 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 mM) 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 mM) 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.

Comprehensive Biological and Chemical Evaluation of Two Seseli Species (S. gummiferum and S. transcaucasicum)

“…Besides, a recent study showed that chlorogenic acid, a main compound identified in the Seseli species in the current study, did not reduce viability of human promyelocytic leukemia cells (HL-60) and human acute T-cell leukemia cells (Jurkat). Furthermore, chlorogenic acid at a concentration of 100 µM induced global DNA hypomethylation, a cell-specific effect in Jurkat cells [71]. Another study showed that chlorogenic acid exhibited cytotoxic activity via hydrogen peroxide-mediated oxidation mechanism in human oral squamous cell carcinoma (HSC-2) and salivary gland tumor (HSG) cell lines [72].…”

Profiling of Polyphenolic Compounds of Leontopodium alpinum Cass Callus Cultures Using UPLC/IM-HRMS and Screening of In Vitro Effects

“…These results could be attributed to the high quantity of polyphenols which are known to modulate pathways relevant to proliferation, migration or colony formation and in some particular cases cell death could be triggered [ 27 , 28 , 29 , 30 ].…”

“…It was also described that it is able to interact with key molecules that can further modulate critical biological pathways involved in cell survival or proliferation [ 34 ]. It was also shown that chlorogenic acid can enhance the antitumor effect of conventional therapeutic agents like doxorubicin by protecting the non-cancer cells against doxorubicin toxicity [ 35 ] or induce hypomethylation of Jurkat cells, being benefic in the case of hematological malignancies [ 27 ].…”

The impact of the co‐exposure of melanoma cells to chlorogenic acid and a moderate‐strength static magnetic field

“…327‐97‐9) at concentrations between 0.001 and 1.5 mmol/L was toxic to the normal fibroblast cell cultures and the melanoma cell cultures. The concentration range was selected on the basis of research on various cell lines (Hernandes et al., 2020; Hou et al., 2017; Sadeghi Ekbatan et al, 2018).…”