Cytotoxicity and DNA binding properties of a chloro glycylhistidinate gold(III) complex (GHAu).
The chloro glycylhistidinate gold(III) complex (GHAu) is shown to be fairly cytotoxic towards the established A2780 ovarian carcinoma human cell line either sensitive or resistant to cisplatin. Remarkably, GHAu is far more cytotoxic than the corresponding zinc(II), palladium(II), platinum(II) and cobalt(II) complexes implying that cytotoxicity is essentially to be ascribed to the presence of a gold(III) center. Circular dichroism (CD) spectra, atomic absorption measurements and DNA melting profiles suggest that GHAu in vitro is able to bind DNA, the presumed target for several antitumor metal complexes, and to modify its conformation, even if the observed changes are generally small. Implications of these findings for the mechanism of action of cytotoxic gold(III) complexes are discussed.
Carotti
S
S
Department of Pharmacology, University of Florence, Italy.
Marcon
G
G
Marussich
M
M
Mazzei
T
T
Messori
L
L
Mini
E
E
Orioli
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000633:toxicity*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D002945:Cisplatin / Q000633:toxicity; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004151:Dipeptides / Q000378:metabolism / Q000633:toxicity*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D050607:Organogold Compounds; D009942:Organometallic Compounds / Q000378:metabolism / Q000633:toxicity*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013054:Spectrophotometry, Atomic; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D004151:Dipeptides; D050607:Organogold Compounds; D009942:Organometallic Compounds; C405883:chloro glycylhistidinate gold(III) complex; D004247:DNA; D002945:Cisplatin