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Intracellular mapping of the distribution of metals derived from the antitumor metallocenes

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Abstract

The intracellular distribution of transition metals in V79 Chinese hamster lung cells treated with subtoxic doses of the organometallic anticancer complexes Cp2MCl2, where Cp is η 5 -cyclopentadienyl and M is Mo, Nb, Ti, or V, has been studied by synchrotron-based X-ray fluorescence (XRF). While significantly higher concentrations of Mo and Nb were found in treated cells compared with control cells, distinct differences in the cellular distribution of each metal were observed. Analysis of thin sections of cells was consistent with some localization of Mo in the nucleus. Studies with a noncytotoxic thiol derivative of molybdocene dichloride showed an uneven distribution of Mo in the cells. For comparison, the low levels of Ti and V in cells treated with the more toxic titanocene and vanadocene complexes, respectively, resulted in metal concentrations at the detection limit of XRF. The results agree with independent chemical studies that have concluded that the biological chemistry of each of the metallocene dihalides is unique.

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Abbreviations

AAS:

Atomic absorption spectroscopy

Cp:

η 5-Cyclopentadienyl

EAT:

Erhlich ascites tumor

GFAAS:

Graphite furnace atomic absorption spectroscopy

ICP:

Inductively coupled plasma

PBS:

Phosphate-buffered saline

SRIXE:

Synchrotron-radiation-induced X-ray emission

XRF:

X-ray fluorescence

References

  1. Köpf-Maier P, Köpf H (1979) Angew Chem Int Ed 18:477–478

    Google Scholar 

  2. Köpf-Maier P, Köpf H (1979) Z Naturforsch 34b:805–807

    Google Scholar 

  3. Köpf-Maier P, Leitner M, Köpf H (1980) J Inorg Nucl Chem 42:1789–1791

    Google Scholar 

  4. Köpf-Maier P, Leitner M, Voigtländer R, Köpf H (1979) Z Naturforsch 34c:1174–1176

    Google Scholar 

  5. Köpf-Maier P, Köpf H (1994) In: Fricker SP (ed) Metal compounds in cancer therapy. Chapman & Hall, London, pp 109–146

  6. Clarke MJ, Zhu F, Frasca DR (1999) Chem Rev 99:2511–2533

    Google Scholar 

  7. Berdel WE, Schmoll HJ, Scheulen ME, Korfel A, Knoche MF, Harstrci A, Bach F, Baumgart J, Sass G (1994) J Cancer Res Clin Oncol 120[Suppl]:R172

    Google Scholar 

  8. Christodoulou CV, Ferry DR, Fyfe DW, Young A, Doran J, Sheehan TMT, Eliopoulos A, Hale K, Baumgart J, Sass G, Kerr DJ (1998) J Clin Oncol 16:2761–2769

    Google Scholar 

  9. Korfel A, Scheulen ME, Schmoll HJ, Gründel O, Harstrick A, Knoche M, Fels LM, Skorzec M, Bach F, Baumgart J, Sab G, Seeber S, Thiel E, Berdel WE (1998) Clin Cancer Res 4:2701–2708

    Google Scholar 

  10. Lümmen G, Sperling H, Luboldt H, Otto T, Rübben H (1998) Cancer Chemother Pharmacol 42:415–417

    Google Scholar 

  11. Kröger N, Kleeberg UR, Mross K, Edler L, Saß G, Hossfeld DK (2000) Onkologie 23:60–62

    Google Scholar 

  12. Köpf-Maier P, Krahl D (1981) Naturwissenschaften 68:273–274

    Google Scholar 

  13. Köpf-Maier P, Krahl D (1983) Chem Biol Interact 44:317–328

    Google Scholar 

  14. Köpf-Maier P, Köpf H (1986) Drugs Future 11:297–320

    Google Scholar 

  15. Köpf-Maier P, Wagner W, Köpf H (1981) Naturwissenschaften 68:272–273

    Google Scholar 

  16. Harding MM, Mokdsi G (2000) Curr Med Chem 7:1289–1303

    Google Scholar 

  17. McLaughlin ML, Cronan Jr JM, Schaller TR, Snelling RD (1990) J Am Chem Soc 112:8949–8952

    Google Scholar 

  18. Zhang Z, Yang P, Guo M (1996) Transition Met Chem 21:322–326

    Google Scholar 

  19. Guo M, Sun H, McArdle HJ, Gambling L, Sadler PJ (2000) Biochemistry 39:10023–10033

    Google Scholar 

  20. Sun H, Li H, Weir RA, Sadler PJ (1998) Angew Chem Int Ed 37:1577–1579

    Google Scholar 

  21. Guo M, Guo Z, Sadler PJ (2001) J Biol Inorg Chem 6:698–707

    Google Scholar 

  22. Kuo LY, Kanatzidis MG, Sabat M, Tipton AL, Marks TJ (1991) J Am Chem Soc 113: 9027–9045

    Google Scholar 

  23. Balzarek C, Weakley TJR, Kuo LY, Tyler DR (2000) Organomet 19:2927–2931

    Google Scholar 

  24. Harding MM, Mokdsi G, Mackay JP, Prodigalidad M, Lucas SW (1998) Inorg Chem 37:2432–2437

    Google Scholar 

  25. Toney JH, Marks TJ (1985) J Am Chem Soc 107:947–953

    Google Scholar 

  26. Harding MM, Prodigalidad M, Lynch MJ (1996) J Med Chem 39:5012–5016

    Google Scholar 

  27. Bertsch PM, Hunter DB (2001) Chem Rev 101:1809–1842

    Google Scholar 

  28. Dillon CT, Lay PA, Kennedy BJ, Stampfl APJ, Cai Z, Ilinski P, Rodrigues W, Legnini DG, Lai B, Maser J (2002) J Biol Inorg Chem 7:640–645

    Google Scholar 

  29. Twining BS, Baines SB, Fisher NS, Maser J, Vogt S, Jacobsen C, Tovar-Sanchez A, Sanudo-Wilhelmy SA (2003) Anal Chem 75:3806–3816

    Google Scholar 

  30. Hall MD, Dillon CT, Zhang M, Beale P, Cai Z, Lai B, Stampfl APJ, Hambley TW (2003) J Biol Inorg Chem 8:726–732

    Google Scholar 

  31. Omega R, Bohic S, Tucoulou R, Somogyi A, Deves G (2004) Anal Chem 76:309–314

    Google Scholar 

  32. Kemner KM, Kelly SD, Lai B, Maser J, O’Loughlin EJ, Sholto-Douglas D, Cai ZH, Schneegurt MA, Kulpa CF, Nealson KH (2004) Science 306:686–687

    Google Scholar 

  33. Waern JB, Dillon CT, Harding MM (2005) J Med Chem 48:2093–2099

    Google Scholar 

  34. Vera JL, Roman FR, Melendez E (2004) Anal Bioanal Chem 379:399–403

    Google Scholar 

  35. Yun W, Lai B, Cai Z, Maser J, Legnini D, Gluskin E, Chen Z, Krasnoperova AA, Vladimirsky Y, Cerrina F, Di Fabrizio E, Gentili M (1999) Rev Sci Instrum 70:2238–2241

    Google Scholar 

  36. Lee H-R, Lai B, Yun W, Mancini D, Cai Z (1997) SPIE Proc 3149:257–264

    Google Scholar 

  37. Vogt S (2003) J Phys IV:Proc 104:635–638

    Google Scholar 

  38. Köpf-Maier P, Köpf H (1988) Struct Bonding 70:103–185

    Google Scholar 

  39. Mosmann T (1983) J Immunol Meth 65:55–63

    Google Scholar 

  40. Tada H, Shiho O, Kuroshima K-I, Koyama M, Tsukamoto K (1986) J Immunol Meth 93:157–165

    Google Scholar 

  41. Graphpad Software (1993) Graphpad Instat, San Diego, CA

  42. Mokdsi G, Harding MM (2001) J Inorg Biochem 83:205–209

    Google Scholar 

Download references

Acknowledgements

This work was supported by the Sydney University Cancer Research Fund and the Australian Synchrotron Research Program, which is funded by the Commonwealth of Australia under the Major National Research Facilities program. The use of APS facilities was supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract no. W-31-109-Eng-38. J.B.W. gratefully acknowledges the receipt of an Australian Postgraduate Award. H.H.H. acknowledges support from an Australian Synchrotron Research Program Postdoctoral Fellowship.

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Authors and Affiliations

  1. School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia

    Jenny B. Waern, Hugh H. Harris & Margaret M. Harding

  2. Department of Chemistry, University of Wollongong, Wollongong, NSW, 2522, Australia

    Carolyn T. Dillon

  3. Experimental Facilities Division, Argonne National Laboratory, Argonne, IL, 60439, USA

    Barry Lai & Zhonghou Cai

Authors
  1. Jenny B. Waern
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  2. Hugh H. Harris
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  3. Barry Lai
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  4. Zhonghou Cai
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  5. Margaret M. Harding
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Correspondence to Margaret M. Harding.

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Waern, J.B., Harris, H.H., Lai, B. et al. Intracellular mapping of the distribution of metals derived from the antitumor metallocenes. J Biol Inorg Chem 10, 443–452 (2005). https://doi.org/10.1007/s00775-005-0649-1

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  • DOI: https://doi.org/10.1007/s00775-005-0649-1

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