The Coffee Constituent Chlorogenic Acid Induces Cellular DNA Damage and Formation of Topoisomerase I鈥?and II鈥揇NA Complexes in Cells
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- 作者：Estefan铆a Burgos-Mor贸n ; Jos茅 Manuel Calder贸n-Monta帽o ; Manuel Luis Orta ; Nuria Pastor ; Concepci贸n P茅rez-Guerrero ; Caroline Austin ; Santiago Mateos ; Miguel L贸pez-L谩zaro
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2012
- 出版时间：August 1, 2012
- 年：2012
- 卷：60
- 期：30
- 页码：7384-7391
- 全文大小：457K
- 年卷期：v.60,no.30(August 1, 2012)
- ISSN：1520-5118
文摘
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 纬- H2AX focus assay) and observed that CGA (0.5鈥? 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.