Study of the biological effects and DNA damage exerted by a new dipalladium-Hmtpo complex on human cancer cells.
The new dipalladium complex [Pd(2)(mu-mtpo-N(3),N(4))(2)(phen)(2)](NO(3))(2) (where phen=1,10-phenantroline; Hmtpo=5,7-dihydro-7-oxo-5-methyl[1,2,4]triazolopyrimidine), (Pd(2)-Hmtpo, or complex I), interacts effectively with DNA plasmid (pBS), as studied by circular dichroism spectroscopy (CD), causing large helix distortions, altering the direction of the main DNA helix axis and producing unwinding of the DNA double helix. DNA damage induced by complex I was highly significant at 2.81 microM (ovarian carcinoma TG cell line), as assessed by comet assay, a dose at which all treated nuclei showed more than 30% DNA migration to the comet tail. DNA damage effect is a consequence of genotoxicity and not a false positive response caused by cytotoxicity. In vitro cytotoxic assay on the two human tumor cell lines TG and BT-20 (breast carcinoma), shows that doses of 0.47, 1.41 and 2.81 microM produce significant antiproliferative effects after 4 days of treatment compared with control. Complex I was highly cytotoxic at 2.81 microM causing an inhibition of viable cells of 65.5%. Cisplatin (cis-DDP) exhibits lower cytotoxic activity in TG cells than dipalladium complex (a cisplatin dose of 6.67 microM inhibits 30.3%) and does not cause migration of DNA to comet tail.
Akdi
Khalid
K
Departamento de Química Inorgánica, Sección de Química Bioinorgánica, Facultad de Química, Universidad de Sevilla, 41012 Seville, Spain.
Vilaplana
Rosario A
RA
Kamah
Sanaa
S
Navarro
Jorge A R
JA
Salas
Juan M
JM
González-Vílchez
Francisco
F
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002942:Circular Dichroism; D002945:Cisplatin / Q000494:pharmacology; D020552:Comet Assay; D004249:DNA Damage; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010165:Palladium / Q000494:pharmacology*; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C460300:dipalladium-Hmtpo; D010165:Palladium; D002945:Cisplatin