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Biologic Activity of a Dinuclear Pd(II)–Spermine Complex Toward Human Breast Cancer
Author(s) -
Fiuza Sónia M.,
Holy Jon,
Batista de Carvalho Luis A. E.,
Marques Maria P. M.
Publication year - 2011
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01081.x
Subject(s) - spermine , breast cancer , human breast , cancer research , chemistry , cancer , medicine , biochemistry , enzyme
A dinuclear palladium‐based complex (Pd 2 ‐Spm) was synthesized and compared with cisplatin (cDDP) on two different human breast cancer cell lines (MCF‐7 and MDA‐MB‐231) as well as toward an untransformed cell line (BJ fibroblasts). The results obtained show that Pd 2 ‐Spm is more effective against the estrogen receptors [ER(−)] cell line MDA‐MB‐231, while cDDP displayed better results for the ER(+) MCF‐7 cell line. It was shown that, like cDDP, Pd 2 ‐Spm triggers phosphorylation of H2AX, indicating that this compound damages DNA. Apart from DNA, Pd 2 ‐Spm also targets the cytoskeleton having a greater impact on cell morphology than cDDP. Pd 2 ‐Spm and cDDP have opposite antiproliferative activities in the presence of the PI3K inhibitor wortmannin. Furthermore, Pd 2 ‐Spm at an optimized concentration displays a rapid antiproliferative effect as opposed to cDDP, which seems to have a slower kinetics. The results point to a distinct mechanism of action for each of these complexes, which may explain their synergistic action when coadministrated.