Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 99, Issue 12, Pages 2387-2394Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2005.09.006
Keywords
platinum(II); pi-complex; circular dichroism; electrophoresis; atomic force microscopy; cytotoxicity; cancer cell lines; A431; Capan-1
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The interaction with DNA and the cytotoxic activity of a new organometallic platinum(II) compound were studied. Different techniques were used to evaluate changes in secondary and tertiary DNA structures, and to obtain images of DNA morphological changes. The ability of platinum complex to modify secondary DNA structure was explored by circular dichroism (CD). Electrophoretic mobility showed changes in tertiary DNA structure. Finally, Atomic Force Microscopy (AFM) revealed morphological changes of plasmid DNA (pBR322). This compound breaks the traditional structure-activity rules for cis-platinum compounds, but it could be of interest because of its different kinetics. An organometallic bond normally shows a higher trans-effect than an amine ligand, and that fact, a priori, could contribute to a higher DNA binding rate. Human A431 and Capan-1 cells (vulvae carcinoma and pancreatic carcinoma, respectively) were exposed to increasing concentrations of cisplatin and complex 6 for 24 h, after which time the cell number/viability was determined by the colorimetric MTT assay. A low cytotoxicity of organometallic compound 6 against A431 and Capan-1 cancer cell lines was observed and this result is consistent with the low interaction with DNA observed in previous studies. (c) 2005 Elsevier Inc. All rights reserved.
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