In vitro cancer chemotherapeutic activity of 1,10-phenanthroline (phen), [Ag2(phen)3(mal)] • 2H2O, [Cu(phen)2(mal)] • 2H2O and [Mn(phen)2(mal)] 2H2O (malH2=malonic acid) using human cancer cells

被引:108
作者
Deegan, Carol
McCann, Malachy
Devereux, Michael
Coyle, Barry
Egan, Denise A. [1 ]
机构
[1] Inst Technol, Sch Sci, Pharma R&D Team, Dublin 24, Ireland
[2] Inst Technol, Sch Sci, Dept Sci, Dublin 24, Ireland
[3] Natl Univ Ireland, Dept Chem, Maynooth, Kildare, Ireland
[4] Inst Technol, Dublin 2, Ireland
关键词
1,10-phenanthroline; metal complexes; cell carcinoma; DNA inhibition; chemotherapeutic potential;
D O I
10.1016/j.canlet.2006.04.006
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The chemotherapeutic potential of 1,10-phenanthroline (phen), and three of its transition metal complexes, namely [Cu(phen)(2)(mal)]center dot 2H(2)O, [Mn(phen)(2)(mal)]center dot 2H(2)O and [Ag-2(phen)(3)(mal)]center dot 2H(2)O (malH(2) = malonic acid) was determined using two human carcinoma cell lines (A-498 and Hep-G2). Phen and the three metal phen complexes induced a concentration-dependent cytotoxic effect, with metal complexes demonstrating the greatest cytotoxic response. In comparative studies, IC50 values show cytotoxicity of between 3 and 18 times greater than that observed for the metal-based anti-cancer agent, cisplatin. All of the phen-based complexes inhibited DNA synthesis which did not appear to be mediated through intercalation. Also, the potential cancer chemotherapeutic application of these compounds was seen to be enhanced by results obtained from Ames tests, which showed all of the test agents and their phase I metabolites were non-mutagenic. Taken together, these results suggest that phen and the three metal-phen complexes may have a therapeutic role to play in the successful treatment and management of cancer. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:224 / 233
页数:10
相关论文
共 32 条
[1]   BACTERICIDAL ACTION OF SELECTED PHENANTHROLINE CHELATES AND RELATED COMPOUNDS [J].
BUTLER, HM ;
HURSE, A ;
THURSKY, E ;
SHULMAN, A .
AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE, 1969, 47 :541-&
[2]   Induction of apoptosis in yeast and mammalian cells by exposure to 1,10-phenanthroline metal complexes [J].
Coyle, B ;
Kinsella, P ;
McCann, M ;
Devereux, M ;
O'Connor, R ;
Clynes, M ;
Kavanagh, K .
TOXICOLOGY IN VITRO, 2004, 18 (01) :63-70
[3]   Mode of anti-fungal activity of 1,10-phenanthroline and its Cu(II), Mn(II) and Ag(I) complexes [J].
Coyle, B ;
Kavanagh, K ;
McCann, M ;
Devereux, M ;
Geraghty, M .
BIOMETALS, 2003, 16 (02) :321-329
[4]   THE UNWINDING OF CIRCULAR DNA BY INTERCALATING AGENTS AS DETERMINED BY GEL-ELECTROPHORESIS [J].
DOUGHERTY, G .
BIOSCIENCE REPORTS, 1983, 3 (05) :453-460
[5]   BIOLOGICAL ACTIONS OF 1,10-PHENANTHROLINE AND 2,2'-BIPYRIDINE HYDROCHLORIDES QUATERNARY SALTS AND METAL CHELATES AND RELATED COMPOUNDS .1. BACTERIOSTATIC ACTION ON SELECTED GRAM-POSITIVE GRAM-NEGATIVE AND ACID-FAST BACTERIA [J].
DWYER, FP ;
REID, IK ;
SHULMAN, A ;
LAYCOCK, GM ;
DIXSON, S .
AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE, 1969, 47 :203-+
[6]  
FRICKER PS, 1994, ROLE METALS CANC THE, P10
[7]   Synthesis and anti-Candida activity of copper(II) and manganese(II) carboxylate complexes -: X-ray crystal structures of [Cu(sal)(bipy)]•C2H5OH•H2O and [Cu(norb)(phen)2]•6.5H2O (salH2 = salicylic acid, norbH2 = cis-5-norbornene-endo-2,3-dicarboxylic acid;: bipy = 2,2′-bipyridine;: phen = 1,10-phenanthroline) [J].
Geraghty, M ;
Sheridan, V ;
McCann, M ;
Devereux, M ;
McKee, V .
POLYHEDRON, 1999, 18 (22) :2931-2939
[8]   Anticancer activity of the lanthanum compound [tris(1,10-phenanthroline)lanthanum(III)]trithiocyanate (KP772;: FFC24) [J].
Heffeter, P ;
Jakupec, MA ;
Körner, W ;
Wild, S ;
von Keyserlingk, NG ;
Elbling, L ;
Zorbas, H ;
Korynevska, A ;
Knasmüller, S ;
Sutterlüty, H ;
Micksche, M ;
Keppler, BK ;
Berger, W .
BIOCHEMICAL PHARMACOLOGY, 2006, 71 (04) :426-440
[9]   Study of cytotoxicity mechanisms of silver nitrate in human dermal fibroblasts [J].
Hidalgo, E ;
Dominguez, C .
TOXICOLOGY LETTERS, 1998, 98 (03) :169-179
[10]   Copper and genomic stability in mammals [J].
Linder, MC .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2001, 475 (1-2) :141-152