Investigation of effects of newly synthesized Pt(II) complex against human serum albumin and leukemia cell line of K562

  • Divsalar, Adeleh (Institute of Biochemistry and Biophysics, University of Tehran) ;
  • Saboury, Ali A. (Institute of Biochemistry and Biophysics, University of Tehran) ;
  • Ahadi, Leila (Institute of Biochemistry and Biophysics, University of Tehran) ;
  • Zemanatiyar, Elham (Institute of Biochemistry and Biophysics, University of Tehran) ;
  • Mansouri-Torshizi, Hassan (Department of Chemistry, University of Sistan & Baluchestan)
  • Received : 2010.09.08
  • Accepted : 2010.10.21
  • Published : 2010.11.30


The biological evaluation of a new synthesized Pt(II)-complex, 2,2'-bipyridin Butylglycinato Pt(II) nitrate, an anti-tumor component, was studied at different temperatures by fluorescence and far UV circular dichroism (CD) spectroscopic methods. Human serum albumin (HSA) and human tumor cell line K562 were as targets. The Pt(II)-complex has a strong ability to quench the intrinsic fluorescence of HSA. Binding and thermodynamic parameters of the interaction were calculated by fluorescence quenching method. Far-UV-CD results showed that Pt(II)-complex induced increasing in content of $\alpha$ helical structure of the protein and stabilized it. The 50% cytotoxic concentration ($Cc_{50}$) of complex was determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay at different incubation times. Also, fluorescence staining with DAPI (4,6-diamidino-2-phenylindole) revealed some typical nuclear changes, which are characteristic of apoptosis. Above results suggest that Pt (II) complex is a promising anti-proliferative agent and should execute its biological effects by inducing apoptosis.


  1. Wang, Y. Q., Zhang, H. M., Zhang, G. C., Tao, W. H. and Tang, S. H. (2007) Binding of brucine to human serum albumin. J. Mol. Struct. 830, 40-45.
  2. Meloun, B., Morávek, L. and Kotska, V. (1975) Complete amino acid sequence of human serum albumin. FEBS Lett. 58, 134-137.
  3. Trynda-Lemiesz, L., Kozøowski, H. and Keppler, B. K. (1999) Effect of cis-, trans-diamminedichloroplatinum(II) and DBP on human serum albumin. J. Inorg. Biochem. 77, 141-146.
  4. Soskic, M. and Magnus, V. (2007) Binding of ring-substituted indole-3-acetic acids to human serum albumin. Bioorg. Med. Chem. 15, 4595-4600.
  5. Kratz, F. (2008) Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J. Control. Rel. 132, 171-183.
  6. Ascenzi, P. and Fasano, M. (2010) Allostery in a monomeric protein: the case of human serum albumin. Biophys. Chem. 148, 16-22.
  7. Zunszain, P. A., Ghuman, J., Komatsu, T. and Tsuchida, E. (2003) The general structure of Albumin is characterized by several long ${\beta}$ (beta) sheets. BMC Struct. Biol. 3, 6-14.
  8. Honore, B. (1990) Conformational changes in human serum albumin induced by ligand binding. Pharmacol. Toxicol. 66, 7-26.
  9. Cheng, F. Q., Wang, Y. P., Li, Z. P. and Dong, C. (2006) Fluorescence study on the interaction of human serum albumin with bromsulphalein. Spectrochim. Acta. Part A. 65, 1144-1147.
  10. Rezaei-Tavirani, M., Moghaddamnia, S. H., Ranjbar, B., Amani, M. and Marashi, S. A. (2006) Conformational study of human serum albumin in pre-denaturation temperatures by differential scanning calorimetry, circular dichroism and UV spectroscopy. J. Biochem. Mol. Biol. 39, 530-536.
  11. Trynda-Lemiesz, L. and Luczkowski, M. (2004) Human serum albumin: spectroscopic studies of the paclitaxel binding and proximity relationships with cisplatin and adriamycin. J. Inorg. Biochem. 98, 1851-1856.
  12. Subramanyam, R., Gollapudi, A., Bonigala, P., Chinnaboina, M. and Amooru, D. G. (2009) Betulinic acid binding to human serum albumin: a study of protein conformation and binding affinity. J. Photochem. Photobiol. B. Biol. 94, 8-12.
  13. Cicheics, R. H. and Kouzi, S. A. (2004) Chemistry, biological activity and chemotherapeutic potential of betulinic acid for the preventation and treatment of cancer and HIV infection. Med. Chem. Res. Rev. 24, 90-114.
  14. Mansouri-Torshizi, H., Srivastava, T. S., Perekh, H. K., Chitnis, M. P. (1992) Synthesis, spectroscopic, cytotoxic, and DNA binding studies of binuclear 2,2'-bipyridine-platinum(II) and-palladium(II) complexes of meso-alpha,alpha'-diaminoadipic and meso-alpha,alpha'-diaminosuberic acids. J. Inorg. Biochem. 45, 135-148.
  15. Giovagnini, L., Marzano, C., Bettio, F. and Fregona, D. (2005) Chemical and biological profiles of novel copper (II) complexes containing S-Donor ligands for the treatment of cancer. J. Inorg. Biochem. 99, 2139.
  16. Zhang, Q., Zhong, W., Xing, B., Tang, W. and Chen, Y. (1998) Binding properties and stoichiometries of a palladium(II) complex to metallothioneins in vivo and in vitro. J. Inorg. Biochem. 72, 195-200.
  17. Mansoori-Torshizi, H., Islami-Moghaddam, M. and Saboury, A. A. (2003) A microcalorimetry and spectroscopy study on the interaction of bovine serum albumin with 2,2’-bipyridine octylglycinato palladium (II) nitrate. Acta. Biochim. Biophys. Sin. 5, 886-890.
  18. Wang, K., Lu, J. F. and Li, R. C. (1996) The events that occur when cisplatin encounters cells. Coord. Chem. Rev. 151, 53-88.
  19. Divsalar, A., Bagheri, M. J., Saboury, A. A., Mansoori-Torshizi, H. and Amani, M (2009) Investigation on the interaction of new designed anti-cancer Pd(II) complexes with different aliphatic tails and Human serum albumin. J. Phys. Chem. B. 113, 14035-14042.
  20. Lakowicz, J. R. (1999) Principles of Fluorescence Spectroscopy, 2nd ed., Kluwer Academic Publishers/Plenum Press, New York, USA.
  21. Ambrosetti, R., Bianchini, R., Fischella, S., Fichera, M. and Zandomeneghi, M. (1996) Resolution of the absorbance and CD spectra and formation constants of the complexes between human serum albumin and methyl orange. Chem. Eur. J. 2, 149-156.
  22. He, X. M. and Carter, D. C. (1992) Atomic structure and chemistry of human serum albumin. Nature 358, 209-215.
  23. Froehlich, E., Mandeville, J. S., Jennings, C. J., Sedaghat-Herati, R. and Tajmir-Riahi, H. A. (2009) Dendrimers bind human serum albumin. J. Phys. Chem. B. 113, 6986.
  24. Divsalar, A., Saboury, A. A., Yousefi, R., Moosavi-Movahedi, A. A. and Mansoori-Torshizi, H. (2006) Spectroscopic aned cytotoxic studies of novel desighned palladium complexes: beta lactoglobulin and K562 as targets. Int. J. Biol. Macromol. 40, 381-386.
  25. Osadebe, P. O., Onugwu, L. E. and Attama, A. A. (2008) Energetics of the interaction between piroxicam and beta-cyclodextrin (CD) in inclusion complexes. Scien. Res. Essay. 3, 86-93.
  26. Hu, Y. J., Liu, Y., Zhao, R. M. and Qu, S. S. (2005) Interaction of colchicine with human serum albumin investigated by spectroscopic methods. Int. J. Biol. Macromol. 37, 122-126.
  27. Liu, X. F., Xia, Y. M. and Fang, Y. (2005) Effect of metal ions on the interaction between bovine serum albumin and berberine chloride extracted from a traditional Chinese Herb coptis chinensis franch. J. Inorg. Biochem. 99, 1449-457.
  28. Mansouri-Torshizi, H., Srivastava, T. S., Perekh, H. K. and Chitnis, M. P. (1992) Synthesis, spectroscopic, cytotoxic, and DNA binding studies of binuclear 2,2'-bipyridine-platinum(II) and -palladium(II) complexes of meso-alpha,alpha'-diaminoadipic and meso-alpha,alpha'-diaminosuberic acids. J. Inorg. Biochem. 45, 135-148.
  29. Mansouri-Torshizi, H., I-Moghaddam, M., Divsalar, A. and Sabory, A. A. (2008) Bipyridinebutyldithiocarbamatoplatinum(II) and palladium(II) complexes: synthesis, characterization, cytotoxicity and rich DNA-binding studies. Bioorg. Med. Chem. 16, 9616-9625.
  30. Divsalar, A., Saboury, A. A., Mansouri-Torshizi, H. and Moosavi-Movahedi, A. A. (2007) Binding Properties of a New Anti-tumor Component (2,2-bipyridin octylglycinato Pd(II) nitrate) with Bovine beta-lactoglobulin-A and –B. J. Biomol. Struct. Dyn. 25, 173-182.
  31. Yang, J. T., Wu, C. S. C. and Martinez, H. M. (1981) Direct determination of absolute circular dichroism data and calibration of commercial instrument. Anal. Chem. 53, 778.
  32. Manavalan, P. and Johnson, C. J. R. (1987) Variable selection method improves the prediction of protein secondary structure from circular dichroism spectra. Anal. Biochem. 167, 76-85.
  33. Kubota, Y., Kubota, K. and Tani, S. (1998) DNA binding properties of DAPI (4',6-diamidino-2-phenylindole) analogs having an imidazoline ring or a tetrahydropyrimidine ring: Groove-binding and intercalation. Nucleic Acids Symposium Series. 44, 53-54.

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