Prooxidant activity of hydroxycinnamic acids on DNA damage in the presence of Cu(II) ions: mechanism and structure-activity relationship.
The prooxidant effect of hydroxycinnamic acids (HCAs), i.e., caffeic acid (CaA), chlorogenic acid (ChA), sinapic acid (SA), ferulic acid (FA), 3-hydroxycinnamic acid (3-HCA) and 4-hydroxycinnamic acid (4-HCA) on supercoiled pBR322 plasmid DNA strand breakage and calf thymus DNA damage in the presence of Cu(II) ions has been studied. It was found that the compounds bearing ortho-dihydroxyl group (CaA and ChA) or bearing 4-hydroxy-3-methoxyl group (SA and FA) exhibited remarkably higher activity in the DNA damage than the ones bearing no such functionalities. The good correlation between the DNA damaging activity and the oxidative potential of the compounds indicates that the electron transfer between HCAs and Cu(II) plays a crucial role in the reaction. UV-Visible spectral changes demonstrated that CaA or ChA can chelate with Cu(II) as a bidentate ligand, hence facilitating intramolecular electron transfer between CaA or ChA and Cu(II). The involvement of reactive oxygen species (ROS) and Cu(I) ions in the DNA damage were affirmed by the inhibition of DNA breakage using mannitol, glutathione (GSH), catalase and bathocuproinedisulfonic acid (BCDS). These results may have important implications regarding the proposed mechanism of apoptosis induced by phenol and endogenous metal ions.
Zheng
Li-Fang
LF
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China.
Dai
Fang
F
Zhou
Bo
B
Yang
Li
L
Liu
Zhong-Li
ZL
D000818:Animals; D002417:Cattle; D003300:Copper / Q000633:toxicity*; D003373:Coumaric Acids / Q000737:chemistry / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D003373:Coumaric Acids; D016877:Oxidants; D003300:Copper