TY - JOUR
T1 - Cytotoxicity of Cu(II) and Zn(II) 2,2′-bipyridyl complexes
T2 - Dependence of IC50 on recovery time
AU - Shi, Yi
AU - Toms, Bonnie B.
AU - Dixit, Namrata
AU - Kumari, Niraj
AU - Mishra, Lallan
AU - Goodisman, Jerry
AU - Dabrowiak, James C.
PY - 2010/8/16
Y1 - 2010/8/16
N2 - We measure the cytotoxicity of three metal complexes containing the 2,2′-bypyridine ligand, Cu(bpy)(NCS)2, 1, [Cu(bpy) 2(H2O)](PF6)2, 2, and Zn(bpy) 2(NCS)2, 3, toward neuroblastoma cells (SK-N-SH) and ovarian cancer cells (OVCAR-3) using two different cell assays. The cells were exposed to various concentrations of the compounds for 1 h and the percent inhibition of cell growth, I, measured for various times after exposure, i.e., as a function of the recovery time t. After developing the theory showing the relationship between I and t, the cytotoxicity data were analyzed to reveal that the two copper complexes, 1 and 2, cause the cells to divide at a slower rate than the controls during the recovery period, but the zinc complex, 3, had little or no effect on cell division during the recovery period. The usual metric for reporting cytotoxicity is IC50, which is the concentration of agent required to inhibit cell growth to 50% of the control population. However, since IC50 can depend on the recovery time, t, as is the case for 1 and 2, reporting IC50 for a single recovery time can hide important information about the long-time effects of a cytotoxic agent on the health of the cell population. Mechanistic studies with the compounds revealed that the copper complexes, 1 and 2, cleave closed circular pBR322 DNA in the presence of ascorbate, while the zinc complex, 3, does not facilitate DNA cleavage under the same conditions. This difference in DNA cleavage activity may be related to the fact that Cu(II) is redox active and can readily change its oxidation state, while Zn(II) is redox inert and cannot participate in a redox cycle with ascorbate to break DNA.
AB - We measure the cytotoxicity of three metal complexes containing the 2,2′-bypyridine ligand, Cu(bpy)(NCS)2, 1, [Cu(bpy) 2(H2O)](PF6)2, 2, and Zn(bpy) 2(NCS)2, 3, toward neuroblastoma cells (SK-N-SH) and ovarian cancer cells (OVCAR-3) using two different cell assays. The cells were exposed to various concentrations of the compounds for 1 h and the percent inhibition of cell growth, I, measured for various times after exposure, i.e., as a function of the recovery time t. After developing the theory showing the relationship between I and t, the cytotoxicity data were analyzed to reveal that the two copper complexes, 1 and 2, cause the cells to divide at a slower rate than the controls during the recovery period, but the zinc complex, 3, had little or no effect on cell division during the recovery period. The usual metric for reporting cytotoxicity is IC50, which is the concentration of agent required to inhibit cell growth to 50% of the control population. However, since IC50 can depend on the recovery time, t, as is the case for 1 and 2, reporting IC50 for a single recovery time can hide important information about the long-time effects of a cytotoxic agent on the health of the cell population. Mechanistic studies with the compounds revealed that the copper complexes, 1 and 2, cleave closed circular pBR322 DNA in the presence of ascorbate, while the zinc complex, 3, does not facilitate DNA cleavage under the same conditions. This difference in DNA cleavage activity may be related to the fact that Cu(II) is redox active and can readily change its oxidation state, while Zn(II) is redox inert and cannot participate in a redox cycle with ascorbate to break DNA.
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U2 - 10.1021/tx100126f
DO - 10.1021/tx100126f
M3 - Article
C2 - 20672868
AN - SCOPUS:77955667739
SN - 0893-228X
VL - 23
SP - 1417
EP - 1426
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 8
ER -