DNA damage induced by resveratrol and its synthetic analogues in the presence of Cu (II) ions: mechanism and structure-activity relationship.
The prooxidant effect of resveratrol (3,5,4'-trihydroxy-trans-stibene) and its synthetic analogues (ArOH), that is, 3,4,4'-trihydroxy-trans-stibene (3,4,4'-THS), 3,4,5-trihydroxy-trans-stibene (3,4,5-THS), 3,4-dihydroxy-trans-stibene (3,4-DHS), 4,4'-dihydroxy-trans-stibene (4,4'-DHS), 2,4-dihydroxy-trans-stilbene (2,4-DHS), 3,5-dihydroxy-trans-stilbene (3,5-DHS) and 3,5,4'-trimethoxy-trans-stibene (3,5,4'-TMS), 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 groups (3,4-DHS, 3,4,4'-THS, and 3,4,5-THS) or bearing 4-hydroxyl groups (2,4-DHS, 4,4'-DHS, and resveratrol) exhibit remarkably higher activity in the DNA damage than the ones bearing no such functionalities. Kinetic analysis by UV-visible spectra demonstrates that the formation of ArOH-Cu (II) complexes, the stabilization of oxidative intermediate derived from ArOH and Cu (II)/Cu (I) redox cycles, might be responsible for the DNA damage. This study also reveals a good correlation between antioxidant and prooxidant activity, as well as cytotoxicity against human leukemia (HL-60 and Jurkat) cell lines. The mechanisms and implications of these observations are discussed.
Zheng
Li-Fang
LF
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China.
Wei
Qing-Yi
QY
Cai
Yu-Jun
YJ
Fang
Jian-Guo
JG
Zhou
Bo
B
Yang
Li
L
Liu
Zhong-Li
ZL
D003300:Copper / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D008954:Models, Biological; D010957:Plasmids / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000494:pharmacology; D000077185:Resveratrol; D013056:Spectrophotometry, Ultraviolet; D013267:Stilbenes / Q000819:agonists / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D017382:Reactive Oxygen Species; D013267:Stilbenes; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; D000077185:Resveratrol