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

J Biol Inorg Chem. 2005 Aug;10(5):443-52. doi: 10.1007/s00775-005-0649-1. Epub 2005 Sep 23.

Abstract

The intracellular distribution of transition metals in V79 Chinese hamster lung cells treated with subtoxic doses of the organometallic anticancer complexes Cp(2)MCl(2), where Cp is eta (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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism*
  • CHO Cells
  • Cricetinae
  • Metals / metabolism*
  • Molecular Structure
  • Molybdenum / chemistry
  • Molybdenum / metabolism*
  • Niobium / chemistry
  • Niobium / metabolism*
  • Organometallic Compounds / metabolism*
  • Spectrometry, X-Ray Emission

Substances

  • Antineoplastic Agents
  • Metals
  • Organometallic Compounds
  • metallocene
  • Niobium
  • Molybdenum