Two closely related nickel complexes have different effects on DNA damage and cell viability.
Nickel is considered a weak carcinogen. It is known to interact with DNA and DNA-binding proteins. The ability of certain nickel compounds to cleave DNA has been exploited mainly for research purposes and less for developing new anticancer drugs. Here we compare the interactions of two closely related nickel complexes, [NiCR]2+ and [Ni(CR-2H)]2+, with DNA. CR stands for 2,12-dimethyl-3,7,11,17-tetraazabicyclo-[11.3.1]-heptadeca-1(17),2,11,13,15-pentaene. [NiCR]2+ has been used in the past as a structure-specific probe for RNA and DNA oligonucleotides in the presence of oxidizing agent but little is known about the biological effects of either complex. Our results show that [Ni(CR-2H)]2+ can damage DNA in vivo and in vitro in the absence of an added oxidizing agent and has an IC50 of 70 microM in human breast cancer cells whereas [NiCR]2+ and NiCl2 do not exhibit significant cytotoxicity. However, both [NiCR]2+ and [Ni(CR-2H)]2+ bind to the minor groove of double-stranded DNA.
Department of Chemistry, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA.
Smita S
SS
Matkar
Lisa A
LA
Wrischnik
Patrick R
PR
Jones
Utha
U
Hellmann-Blumberg
D000818:Animals; D016466:CHO Cells; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000633:toxicity; D009942:Organometallic Compounds / Q000737:chemistry / Q000633:toxicity*
C510397:(2,12-dimethyl-3,7,11,17-tetraazabicyclo(11.3.1)heptadeca-1(17),2,6,11,13,15-hexaenato)nickel(II); D002273:Carcinogens; D007364:Intercalating Agents; D009942:Organometallic Compounds; C090497:nickel(II) (2,12-dimethyl-3,7,11,17-tetraazabicyclo(11.3.1)heptadeca-1(17),2,11,13,15-pentaene) perchlorate; D004247:DNA