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A platinum blue complex exerts its cytotoxic activity via DNA damage and induces apoptosis in cancer cells
Author(s) -
Adiguzel Zelal,
OzalpYaman Seniz,
Celik Gokalp,
Salem Safia,
BagciOnder Tugba,
Senbabaoglu Filiz,
Cetin Yüksel,
Acilan Ceyda
Publication year - 2017
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/cbdd.12940
Subject(s) - dapi , apoptosis , dna fragmentation , dna damage , cancer cell , microbiology and biotechnology , agarose gel electrophoresis , chemistry , cytotoxic t cell , dna , programmed cell death , in vitro , biochemistry , biology , cancer , genetics
Here, we describe the characteristics of a Pt‐blue complex [Pt 4 (2‐atp) 8 (H 2 O)( OH )] (2‐atp: 2‐aminothiophenol) as a prodrug for its DNA ‐binding properties and its use in cancer therapy. The nature of the interaction between the Pt‐blue complex and DNA was evaluated based on spectroscopic measurements, the electronic absorption spectra, thermal behavior, viscosity, fluorometric titration, and agarose gel electrophoresis. Our results suggested that the compound was able to partially intercalate DNA and appeared to induce both single‐ and double‐stranded breaks ( DBS ) on DNA in vitro, but no DSB s in cells. The ability of the compound to induce DNA damage was dependent on reactive oxygen species ( ROS ) in vitro. There was also elevated formation of ROS and SOD expression in response to drug treatment in cell culture. The complex was found to be more cytotoxic to cancer cells in comparison with noncancer controls using WST ‐1 assay. The mean of cell death was determined to be apoptosis as assessed via biochemical, morphological, and molecular observations, including DNA condensation/fragmentation analysis, live cell imaging microscopy, TUNEL analyses, and increase in the levels of pro‐apoptotic genes such as Bag3, Bak, Bik, Bmf, and Hrk. Hence, the Pt‐blue complex under study grants premise for further studies.