Vol.:(0123456789) 1 3 J Biol Inorg Chem DOI 10.1007/s00775-017-1488-6 ORIGINAL PAPER In vitro and in vivo anti‑proliferative evaluation of bis(4′‑(4‑tolyl) ‑2,2′:6′,2″‑terpyridine)copper(II) complex against Ehrlich ascites carcinoma tumors Dharmasivam Mahendiran 1  · Raju Senthil Kumar 2  · Vijayan Viswanathan 3  · Devadasan Velmurugan 3  · Aziz Kalilur Rahiman 1   Received: 26 May 2017 / Accepted: 20 August 2017 © SBIC 2017 Graphical abstract The bis(4′ ‑(4‑tolyl)‑2,2′ :6′ ,2″ ‑ terpyridine)copper(II) complex induces EAC cell apopto‑ sis through a ROS‑mediated mitochondrial pathway and signifcantly reduced the body weight and solid tumor volume in Swiss albino mice. Keywords Apoptosis · Cellular uptake · ROS generation · Western blot · Ehrlich ascites carcinoma (EAC) Introduction In 1978, the Food and Drug Administration (FDA, USA) has approved the platinum-based drug cisplatin for the treatment of cancer. Cisplatin is the most efective chemotherapeu- tic drug, which exhibit 90% cure for the testicular cancer, also treated for head and neck, lung, colorectal and ovarian cancers [1, 2]. However, the use of cisplatin is limited due to their severe side efects, low water solubility and drug resistance [3]. After the discovery of cisplatin, there has been remarkable development in research related with metal Abstract The bis(4′ -(4-tolyl)-2,2′ :6′ ,2″ -terpyridine) copper(II) complex [Cu(ttpy) 2 ]Cl 2 was synthesized and authenticated by single crystal analysis, which shows dis- torted octahedral geometry around copper(II) ion. The crys- tal packing is stabilized by C–H···π inter and intramolecu- lar interactions. The complex was found to be lipophilic as determined by shake-fask method. In vitro cytotoxicity of the complex was tested against Ehrlich ascites carcinoma (EAC) and L6 myotube cell lines. The complex exhibit potent cytotoxicity with respect to the commercially avail- able anticancer drug cisplatin. Hoechst 33258, AO/EB and PI (fow cytometry) staining methods suggest that the com- plex can induce apoptosis in EAC cells. Cell cycle analyses also support the induced apoptosis. Cellular uptake studies revealed that the complex can go into the cytoplasm and accumulate in the cell nuclei. The complex induces EAC cell apoptosis through a ROS-mediated mitochondrial pathway by activating caspase 3 and caspase 7 and regulates the Bcl-2 family proteins. In vivo study of the complex was validated against the animal tumor growth (EAC) cell in Swiss albino mice. Electronic supplementary material The online version of this article (doi:10.1007/s00775-017-1488-6) contains supplementary material, which is available to authorized users. * Aziz Kalilur Rahiman akrahmanjkr@thenewcollege.in; akrahmanjkr@gmail.com 1 Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai 600 014, India 2 Department of Pharmaceutical Chemistry, Swamy Vivekanandha College of Pharmacy, Elayampalayam, Tiruchengodu 637 205, India 3 CAS in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025, India