The coffee constituent chlorogenic acid induces cellular DNA damage and formation of topoisomerase I- and II-DNA complexes in cells.
Chlorogenic acid (CGA) is a plant polyphenol with known antioxidant properties. Although some studies suggest that CGA has anticancer properties, others indicate that this dietary constituent may cause DNA damage and induce carcinogenic effects. Because CGA is widely consumed in the form of coffee, it is important to further evaluate the putative DNA-damaging activity of CGA. Here we have employed two standard techniques commonly used for DNA damage detection (the comet assay and the γ- H2AX focus assay) and observed that CGA (0.5-5 mM) induces DNA damage in normal and cancer cells. We report for the first time that CGA induces high levels of topoisomerase I- and topoisomerase II-DNA complexes in cells (TARDIS assay). Catalase pretreatment abolished the formation of these topoisomerase-DNA complexes and reduced the cytotoxic activity of CGA, therefore indicating that hydrogen peroxide plays an important role in these activities. Lung cancer cells (A549) were more sensitive than normal lung fibroblasts (MRC5) to the cytotoxic activity of CGA, supporting previous findings that CGA may induce selective killing of cancer cells. Taking into consideration our results and the pharmacokinetic profile of CGA, the possible cancer preventive, carcinogenic and therapeutic potential of this dietary agent are discussed.
Department of Pharmacology, Faculty of Pharmacy, University of Seville , Seville, Spain.
Estefanía
E
Burgos-Morón
José Manuel
JM
Calderón-Montaño
Manuel Luis
ML
Orta
Nuria
N
Pastor
Concepción
C
Pérez-Guerrero
Caroline
C
Austin
Santiago
S
Mateos
Miguel
M
López-Lázaro
D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D000975:Antioxidants / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002726:Chlorogenic Acid / Q000493:pharmacokinetics*; D003069:Coffee / Q000737:chemistry*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide; D020014:K562 Cells
D000970:Antineoplastic Agents; D000975:Antioxidants; D003069:Coffee; D002726:Chlorogenic Acid; D006861:Hydrogen Peroxide; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II