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Article Citation - WoS: 7Citation - Scopus: 6A platinum blue complex exerts its cytotoxic activity via DNA damage and induces apoptosis in cancer cells(Wiley, 2017) Adiguzel, Zelal; Ozalp-Yaman, Seniz; Celik, Gokalp; Salem, Safia; Bagci-Onder, Tugba; Senbabaoglu, Filiz; Acilan, CeydaHere, we describe the characteristics of a Pt-blue complex [Pt-4(2-atp)(8)(H2O)(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 DSBs 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.Article Citation - WoS: 4Citation - Scopus: 4Anticancer Investigation of Platinum and Copper-Based Complexes Containing Quinoxaline Ligands(Elsevier, 2022) El-Beshti, Hager Sadek; Yildizhan, Yasemin; Kayi, Hakan; Cetin, Yuksel; Adiguzel, Zelal; Gungor-Topcu, Gamze; Ozalp-Yaman, SenizThis research focuses on synthesis and anticancer activity of trans-[(dichloro)bisdipyridlquinoxalino] and [(dichloro)bisdithienylquinoxalino]copper(II)/platinum(II) compounds as prodrug candidates. The binding interaction of these compounds with calf thymus DNA (CT-DNA) and human serum albumin (HSA) of the complexes were assessed with UV titration, thermal decomposition, viscometric, and fluorometric measurements. The nature of the binding of the complexes on DNA were revealed as electrostatic interaction between the cationic metal complexes ion and the negative phosphate groups of CT-DNA upon removal of the counter ion, chloride. In addition, our complexes induced a surface contact through the hydrophobic region of protein. Antitumor activity of the complexes against human glioblastoma A172, LN229, and U87 cell lines and human lung A549, human breast MDA-231, human cervix HeLa, and human prostate PC-3 cell lines were investigated by examining cell viability, oxidative stress, apoptosis, and migration/invasion. Cytotoxicity of the complexes was evaluated by MTT test. The U87 and HeLa cells were investigated as the cancer cells most sensitive to our complexes. The exerted cytotoxic effect of dipyridlquinoxalino and dithienylquinoxalino copper(II)/platinum(II) complexes was attributed to the formation of the reactive oxygen species in vitro. It is clearly demonstrated that trans-[(dichloro)bisdithenylquinoxalino]copper (II) (Cu(dtq)) has the highest DNA degradation potential and anticancer effect among the tested complexes by leading apoptosis. Wound healing and invasion analysis results also supported the anticancer activity of Cu(dtq). (C) 2021 Elsevier B.V. All rights reserved.
